Autophagy: A Multipotentialite

Tanvi Yalamanchili


Autophagy is an important cellular process involved in cellular health and disease. This review addresses the major mechanisms of autophagy and explores how this process contributes to numerous human diseases. Research suggests that infection by SARS-CoV2, the virus that causes the novel human coronavirus disease COVID-19, may be mediated by autophagy. This paper reviews the role of autophagy in COVID-19 and explores how modulating autophagy may be useful therapeutically.


A multipotentialite is a person with many interests or pursuits. Similarly, autophagy can both promote cell survival and cell death in a context-dependent manner. Autophagy translates to “self-eating.” The primary function of autophagy is to maintain cellular homeostasis — the metabolic equilibrium necessary for a cell to maintain its life functions. Autophagy can be triggered in response to different stimuli, including but not limited to nutrient deprivation, oxidative stress, hypoxia, protein aggregation, or toxic substances[[1]]. It is a process by which damaged organelles or proteins are broken down into basic components to be recycled into new molecules and structures[[2]]. The degradation of these substances occurs in the lysosome, an acid-filled, membrane-bound organelle that breaks apart proteins and organelles. The lysosome contains hydrolases, enzymes that work at low pH levels and use water to break covalent bonds[[3]].
Macroautophagy, microautophagy, and chaperone-mediated autophagy are three types of autophagy[1]. Microautophagy is a lysosomal degradation process that directly engulfs substrates in the cytosol using autophagic tubes.[[4]] Chaperone-mediated autophagy is a process that selectively degrades proteins in lysosomes by delivering them to the lysosomal surface using cytosolic chaperone proteins[[5]]. In macroautophagy, a double membrane vesicle, called an autophagosome, is formed to carry cargo to the lysosome for degradation[[6]]. Autophagy can be further divided based on the substrate being degraded. For instance, mitophagy and nucleophagy denote the degradation of mitochondria and the nucleus, respectively[[7]]. Macroautophagy is often used synonymously with autophagy, and this terminology will be used throughout this review.
Autophagy has been found to play a major role in diseases including cancer, cardiomyopathy, diabetes, and neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Understanding how these different “pursuits” of autophagy contribute to disease may help us determine whether inhibiting or inducing autophagy could be used in disease therapy[1]. A significant disease currently plaguing our world is COVID-19, which is caused by the novel coronavirus SARS-CoV2. Emerging evidence suggests that autophagy plays an important role in the development of COVID-19. This review aims to explain how autophagy mediates COVID-19 progression and discuss how modulating autophagy might be useful therapeutically. However, the development of therapies that induce or inhibit autophagy is hindered by the fact that much remains unknown about autophagy[[8]]. For instance, although it is known that autophagy can both cause and prevent cell death, the signals or situations that initiate a cell death or survival response, as well as the molecular machinery required, remain poorly investigated. This review of autophagy hopes to explain the basics of autophagy, explore the importance of this process in the etiology and treatment of diseases, and investigate how scientists might answer open questions about autophagy to better understand its applications.

Autophagy: Background

Autophagy is a metabolic process. ‘Metabolism’ refers to the network of chemical reactions required for cells to maintain life. Autophagy degrades complex structures into smaller molecular components within the lysosome. These components will then be reused to build new structures when the cell is in stress. Because autophagy breaks down macromolecules, it is considered a ‘catabolic’ process[[9]]. Conversely, inhibiting autophagy promotes ‘anabolism,’ or the process of building new macromolecules from basic components. Many different protein complexes regulate autophagy, and phosphorylation plays a key role in facilitating this cascading process. Protein phosphorylation is the attachment of a phosphate group to the amino acid residues of a protein, which then changes the properties of the protein. Phosphorylation is important for regulating protein function and signaling pathways[[10]].
Because the degraded components are reused as nutrition when the cell is in stress, autophagy can promote the survival of the cell. On the other hand, there is evidence of the accumulation of autophagosomes and autolysosomes in dying cells, suggesting that autophagy can also lead to cell death[[11]]. Nevertheless, the fact that autophagy works together with other forms of cell death like apoptosis and necrosis makes it difficult to differentiate the specific role of autophagy in cell death[[12]]. Apoptosis is a form of cell death that activates caspase proteins to break the cell into small packages from within, which are then engulfed by other cells[[13]]. In necrosis, the cell dies when its membrane ruptures and intracellular contents leak out, potentially damaging neighboring cells and triggering inflammation[11].
There are three different roles that autophagy can play in cell death. One is autophagy-associated cell death, wherein autophagy accompanies other cell death processes but plays no active role in cell death itself. The next is autophagy-mediated cell death, in which a signal triggers autophagy, which then triggers apoptosis, leading to cell death. The third type is autophagy-dependent cell death, which relies on autophagy for regulated cell death[2] and occurs independent of either apoptosis or necrosis.
A unique model that provides evidence of autophagy-dependent cell death is the amoeba Dictyostelium discoideum. This amoeba contained no apoptotic machinery but was still able to carry out cell death. During the amoeba’s transition from vegetative state to fruiting body, autophagy was seen to occur initially in response to the signal of starvation, but only when an additional signal triggered the process did pro-survival autophagy promote cell death[11]. An organism frequently used in the study of autophagy is Drosophilia melanogaster, the fruit fly, because of the model system’s low cost, quick generation, useful genetic tools, and relatively simple anatomy compared to humans[[14]]. Evidence for autophagy-dependent cell death can be seen in the degradation of the Drosophila larval midgut, the main organ that digests and absorbs nutrition[[15]]. The larval midgut degrades normally even in the absence of apoptosis, but this process is delayed if autophagy is inhibited. In this study, cells died by autophagy, as evidenced by the accumulation of autophagic vesicles[[16]]. This observation suggests that the hyperactivation of autophagy promotes cell death. Another mechanism by which cells could die by autophagic-dependent cell death is through autophagy selectively degraded components necessary for the cell to die; degrading these substrates that are necessary for survival would induce cell death[[17]].

Autophagy: How it Works

Process: The cascading autophagic process is mediated by Autophagy-related genes (Atg) that encode the ATG family of proteins, which recruit each other in sequence. In total, autophagy occurs in five stages.
The first step of autophagy is the initiation phase. This process begins at the endoplasmic reticulum (ER), an organelle involved in the production of lipids and proteins. A C-shaped membrane buds off of the ER to form what is known as a pre-autophagosome. This process requires the activation of a protein complex that includes ULK1, Atg13, Fip200, and Atg101. ULK1, or Unk-51-like-kinase, is required for the inception of macroautophagy and the initial formation of the pre-autophagosome (Figure 1)[[18]].

Figure 1: Autophagy Process
Second, in the nucleation phase, the pre-autophagosome elongates. This process requires a protein complex comprised of Vps34 (vacuole ER protein sorting 34), Vps15, and Beclin1 (Figure 1). Beclin1 is activated by ULK1 through phosphorylation. This protein complex converts membrane phospholipids known as phosphatidylinositol bisphosphonates (PIP2) into phosphatidylinositol triphosphates (PIP3)[[19]]. In turn, PIP3 recruits WIPI proteins to the pre-autophagosome. WIPI proteins are a family of proteins essential for interaction with the phospholipids that form the autophagosomal membranes[[20]].
As more WIPI proteins are recruited, the double-membrane vesicle enters the elongation phase, and additional proteins including p62 (ubiquitin-binding cargo protein) and NBR1 act as selective receptors of the different substrates to be degraded. The protein complex consisting of Atg16, Atg5, and Atg12 also help target substrates and proteins instrumental in developing the autophagosome. A crucial protein in the substrate selection of macroautophagy is LC3-I, which comes from pro-LC3 cleaved by Atg4. When LC3-I is targeted to the autophagosome, Atg7 activates it while Atg3 and the phospholipid phosphatidylethanolomine (PE) conjugate to it and convert LC3-I into LC3-II, the lipidated form of LC3[[21]]. Meanwhile, the autophagosome continues to elongate and develops into what is known as a mature autophagosome (Figure 1).
The autophagosome is then attached to microtubules, which are key parts of the cellular “skeleton,” also known as the cytoskeleton, and function in cell structure, motility, and intracellular transport. Autophagosomes are then transported to the perinuclear region, which is the cytoplasmic area around the nucleus of the cell, where the lysosome is present. LC3-II helps facilitate the fusion of the vesicle with the lysosomal organelle. The autophagosome fuses to the lysosome, forming an autolysosome using SNARE proteins[[22]]. SNARE proteins facilitate the fusion between transport vesicles in the cell, like autophagosomes, and the target membrane, in this case, the lysosomal membrane[[23]]. When the autophagosome and lysosomal membranes fuse together, the substrates within the autophagosome spill into the acidic lysosome to be degraded in one of two ways (Figure 1). The autophagic substrates may be degraded by lysosomal hydrolases, which break covalent bonds and are only active at low pH. The acidic environment of the lysosome is maintained by vATPase, a proton-pumping membrane complexe that releases hydrogens into the lysosome[[24]]. Alternatively, substrates may be degraded by lysosomal proteases such as cathespin B and L[[25]]. The degraded material is then recycled through nutrient transporters and is used to fuel the growth of the cell, maintaining homeostasis.
Regulation and Inhibition:
Several important proteins that regulate cell metabolism control the activation of autophagy. An important regulator of this process that activates ULK1 is AMPK, a protein that senses nutrient levels and the energy status of the cell by checking the amount of ATP. On the other hand, the protein complex mTORC1, a master regulator of cellular metabolism, blocks autophagy by inhibiting ULK1 through phosphorylation[18]. Together, AMPK and mTORC1- control when autophagy is initiated by sensing amino acids and nutrient levels. Changes in the activity or expression of these two proteins could either inhibit or induce autophagy, depending on whether autophagy is needed to promote cell death or cell survival[21]. mTORC1 is a switch towards anabolic pathways, meaning it causes the building of new biomasses, while autophagy is a catabolic process, meaning it breaks down biomasses. AMPK functions as a switch towards catabolic pathways, which is why it is an autophagy inducer[[26]]. The induction of autophagy is important when anabolic capacity is low, so that the cell can make nutrients it needs and maintain homeostasis, even when amino acids are scarce. However, activating autophagy when the cell already contains sufficient energy and nutrients would not be favorable since this would cause the unnecessary consumption of macromolecules.
Currently, there aren’t many approved drugs that can regulate autophagy, but there are some molecules used in the lab that can inhibit or activate autophagy. Autophagy can be activated by inhibiting mTOR, such as with the small molecule rapamycin. Autophagy can also be promoted by upregulating AMPK, with approved drugs such as metformin[[27]]. On the other hand, the bioactive compound chloroquine is an inhibitor of autophagy that impairs the fusion of autophagosomes with lysosomes[[28]].

Autophagy: Its Role in Diseases

As a regulator of cellular homeostasis, autophagy plays an important role in health and diseases like aging, diabetes, obesity, neurodegenerative disorders, and even cancer. Autophagy aids in removing infectious agents like bacteria and viruses from host cells[[29]]. However, there are exceptions where autophagy can instead promote disease.
During aging, the ability of cells to combat environmental stresses that impair cellular homeostasis decreases, rendering organisms more prone to diseases of old age. As mentioned before, autophagy’s primary function is to maintain homeostasis, so autophagy is important in increasing lifespan. This has been evidenced in roundworms, whose lifespan is diminished when autophagy proteins are inactivated[[30]]. Inducing autophagy can degrade damaged and misfolded proteins, which accumulate in aging due to the loss of protein homeostasis[[31]]. Inducing autophagy, such as inhibiting mTOR, an inhibitor of autophagy, could potentially increase longevity (Figure 2). The effect of inhibiting mTOR using the drug rapamycin was seen to increase the lifespan in both mice and fruit flies[[32],[33]].

Figure 2: Role of Autophagy in Diseases
Impairment of autophagy also contributes to diabetes and obesity. Defective mitochondria contribute to adiposity, or the condition of being severely overweight; therefore the autophagic degradation of mitochondria by mitophagy can eliminate damaged mitochondria to prevent obesity[[34]]. Similarly, autophagy-deficient pancreatic cells susceptible to ER stress progressed diabetes. However in this system the restoration of Atg7 expression limited ER stress and raised insulin, a hormone that regulates metabolism by increasing cellular glucose uptake[1]. Cells treated with an autophagy inhibitor or depleted of Atg7 accumulated protein aggregates in the presence of high glucose. This suggests that autophagy-deficient cells contribute to the development of diabetes, which means that inducing autophagy could help reverse diabetes (Figure 2).
Accumulation of abnormal protein aggregates in neural cells lead to neurodegenerative disorders such as Alzheimer’s Disease. Protein aggregates can be degraded through autophagy to prevent such diseases from progressing[1]. Parkinson’s disease is a progressive nervous system disorder that causes stiffness or slowing of movement. It is thought to be caused by the accumulation of misfolded proteins and the presence of Lewy bodies, clumps of proteins within the nucleus of neurons[[35]]. Autophagy could represent a mechanism to target and degrade these protein aggregates and help reduce the effect of Parkinson’s. Alzheimer’s disease involves the deterioration of brain cells, inevitably leading to dementia. This disease is thought to be caused by the accumulation of the proteins Tau and amyloid B-peptide. Autophagy plays an important role in removing aggregated tau proteins and inducing the autophagic pathway reduces B-amyloid peptide[[36]]. Huntington’s disease is another neurodegenerative disorder caused by mutations in the genes that result in the aggregation of huntingtin (HTT) proteins. Inducing autophagy can clear these aggregated proteins and slow disease progression (Figure 2)[[37]].
In cancer, autophagy plays a dual role. Although autophagy initially suppresses benign tumor growth, after the cancer reaches more advanced stages, autophagy may promote cancer growth (Figure 2)[21]. During tumor initiation, autophagy acts as a tumor-suppressor by removing cells and organelles damaged by stressful growth conditions in tumors. However, during the later stages of tumor cell growth, autophagy promotes the growth of cancer cells in harsh microenvironmental conditions and helps the tumor survive during chemotherapy[9]. The cause for this switch in the role of autophagy still remains unknown, but nutrient deprivation, limited energy, and hypoxia in tumors may induce autophagy. Inducing autophagy could be an approach to treating cancer, but well-validated drugs or compounds that induce autophagy are limited[21]. When tested in mice, short-term autophagy inhibition caused tumors to shrink dramatically. However, these mice developed fatal neurodegeneration, likely due to the important role of autophagy in preventing neurodegenerative disorders. These findings suggest that there could be a therapeutic window of autophagy inhibition to reduce tumor growth before neurodegenerative disorders develop[21].

COVID-19: An Overview

COVID-19 (Coronavirus Disease-2019) was caused by the novel coronavirus SARS-CoV2. SARS-CoV2 was first recorded in Wuhan, China, followed by outbreaks in many cities within China and across the world. Coronaviruses are single-strand RNA viruses with an envelope made of a lipid membrane studded with protein ‘spikes’ on its surface. Coronaviruses are known to cause severe respiratory diseases in humans[24]. Prior coronavirus outbreaks include Severe Acute Respiratory Syndrome (SARS) in Asia in 2003, and Middle East Respiratory Syndrome (MERS) in Saudi Arabia in 2012[24].
COVID-19 is a zoonotic virus, meaning that it originated in a non-human animal. It was initially thought that COVID-19 could only spread to humans from the original contaminated source, i.e. the infected animal. However it soon became clear that the virus could spread through person-to-person transmission[[38]]. SARS-CoV2 binds to the human angiotensin-converting enzyme 1 (hACE2), which is a cellular receptor expressed mainly on cells of the lower respiratory tract. Clinically, the virus affects the respiratory, gastrointestinal, musculoskeletal, and neurological systems; symptoms are diverse, including fever, cough, shortness of breath, loss of sense of smell or taste, gastrointestinal issues, and brain fog[38].
The coronavirus attaches to the host cell using transmembrane spike (S) glycoproteins, proteins that make up the characteristic ‘spikes’ that give the virus its name (‘corona’, from the Latin term for ‘crown’). The S protein is composed of two subunits that are responsible for viral entry into cells: the S1 subunit and S2 subunit. While the S1 subunit is responsible for binding to the host cell ACE2 receptor, the S2 subunit is required for the fusion of the viral and cellular membranes[[39]]. The ‘spikes’ on the virus act like a key that opens the ACE2 receptor ‘lock’ on the host cell membrane.

Figure 3: Coronavirus and Endocytosis
The virus then enters the host cell through endocytosis, which literally translates to ‘movement into the cell’. During endocytosis, part of the cell membrane (with the virus and receptors attached at the surface) gets pulled inside the cell to form a double membrane vesicle called an endosome (Figure 3)[24]. This process is known as retrograde transport. Some viruses would then travel to the cell’s nucleus where it would replicate its genetic material; however, a coronavirus does not integrate itself into the host cell’s genome. Rather, it hijacks the function of host ribosomes to translate its genome into viral proteins. Ribosomes are organelles that link amino acids together in the order specified by the messenger RNA molecules to synthesize the polypeptide chains that form proteins. Therefore, the coronavirus can utilize host ribosomes to translate viral proteins such as the S protein[[40]]. The viral structural proteins are then inserted into the ER, where they move into the Golgi apparatus, an organelle that packages proteins and transports them in membrane-bound vesicles[[41]]. In the Golgi apparatus, the proteins bind together to assemble into a new virus[[42]]. An endosome, a cellular packaging structure, then carries the virion to the host cell’s membrane and releases new coronavirus through exocytosis.[[43]] In several cases, some S proteins that were not used for assembly travel to the cell’s surface to mediate cellular fusion with adjacent, uninfected cells, spreading the virus.
New research shows that SARS-2 coronaviruses can exit infected cells through the lysosome, and freely spread through the body, thus deactivating the lysosome’s disease-fighting machinery. After performing experiments using imaging and virus-specific markers, researchers discovered that the virus de-acidifies the lysosome to weaken its function and harm the cell’s immune function[[44]].
As of December, several SARS-CoV2 vaccines are headed for FDA approval. Scientists are looking for different ways that vaccines or drugs could help attack the coronaviruses or slow coronavirus spread through the body. They are also working toward the prospect of creating a vaccine that would contain trace amounts of the viral mRNA to provoke the body’s immune system to attack the virus[[45]]. If an immunized person were to become infected with SARS-CoV2, their body would produce antibodies that attach to the spike proteins of the virus and prevent it from attaching to healthy cells. Other scientists suggest targeting the viral translation process at the ribosomes to prevent the virus from replicating its proteins[[46]]. However, each step in developing a vaccine or therapy takes months, if not years, to prove its safety and efficacy, so these therapies may be years away. At the same time, the severity of the ongoing pandemic has dramatically accelerated the research, development, and drug approval process, so these novel therapies may be introduced into the clinic quickly.

Autophagy and Coronavirus

Because autophagy regulates homeostasis, it plays an important role in many diseases, and one of those diseases could be COVID-19. Autophagy could potentially degrade viral particles. Alternatively, autophagy inhibition may be necessary for viral assembly. Although the role of autophagy in SARS-CoV-2 infection has not been widely studied, autophagy has been shown to mediate pathogenicity (infectiousness) of other coronaviruses.
For example, evidence showed that SARS-CoV and MERS-CoV infection blocked fusion between autophagosomes and lysosomes[24]. Certain proteins in the MERS-CoV genome are known to limit autophagy, such as: NSP6, an inhibitor of the elongation of autophagosomes; p4b, an inhibitor of the autophagy activator RNAse L; and p5, an inhibitor of IFN-beta induction, which is linked to autophagy. In a study investigating the effect of MERS-CoV on autophagy, deletion of p4b and p5 proteins reduced the growth of the virus[[47]]. Not only does MERS-CoV inhibit autophagy to avoid being degraded, but it also does so to increase membrane availability for forming double-membrane vesicles, compartments where viral genome replication and transcription occur[46].
Conversely, inducing autophagy can reduce the replication of coronaviruses. Some molecules that induce autophagy are effective at reducing coronavirus replication rate. In fact, MERS-CoV can replicate efficiently only when inhibiting autophagy[[48]]. Because autophagy degrades damaged or diseased components to maintain cellular homeostasis, the cells are incentivized to dispose of viruses using this method, so viruses must inhibit autophagy to continue their replication process. In response to RNA virus infections like COVID-19, the innate immune system can activate autophagy to facilitate clearance of viruses and infected cells[[49]].
Originally thought to be an inducer of autophagy, chloroquine was proposed as a therapeutic agent against COVID-19. However, studies showed chloroquine actually inhibited autophagy by impairing the formation of the autolysosome[21], which would increase the rate of viral replication. Although a recent study showed that chloroquine could not enhance autophagy on its own, when combined with azithromycin, an antibiotic that also has an ‘off target’ effect as an inhibitor of mTOR, the combined treatment induced autophagy[28]. This study could be flawed because the investigators assumed chloroquine (CQ) was responsible for any benefit in patients, while it might have instead been an “off target” effect of azithromycin. The study did not include appropriate controls such as an azithromycin-only treatment group to test the effect of CQ on COVID. In order to further test the implications of this study, testing the effect of azithromycin alone on autophagy compared with an untreated control could better uncover the role of chloroquine and azithromycin as autophagy activators, which could then be used as drugs in experiments to test the effect of autophagy on COVID treatment.
Another potential therapeutic being tested involves the SKP2 protein. SKP2 is a protein that regulates the autophagic process by degrading the pro-autophagic protein Beclin-1[33]. The MERS virus activates SKP2 to slow autophagy and decrease viral degradation[47]. Inhibiting SKP2 shows promising results as a therapeutic treatment against MERS by increasing Beclin-1 and therefore autophagy. The assembly of SNARE proteins would also increase and enhance autophagy, reducing MERS-CoV replication. FDA-approved drugs that inhibit SKP2 include niclosamide and pyrvinium[33]. When researchers treated MERS-infected cells with SKP2 inhibitors in order to stimulate the degradation process, they observed decreased viral infection[37]. Although the exact role of autophagy in the MERS-CoV life cycle is still unknown, further research needs to be done and researching the effect of inhibiting SKP2 in SARS-CoV-2 could be helpful in finding a treatment for COVID-19.
One hypothesis researchers could continue to explore is that suggesting autophagy activators could be used therapeutically to treat COVID-19. One way activating autophagy could inhibit SARS-CoV-2 infection is through degrading the Ace2 receptor to prevent the virus from binding to healthy cells and spreading the disease across organs. Another way could be through the degradation of ribosomes, also known as ribophagy, to prevent SARS-CoV-2 replication, which would inhibit the spread of the virus to healthy cells outside the host cell. Autophagy-dependent cell death could also be a potential treatment; inducing autophagy in infected cells to degrade particles important for cellular survival can lead to cell death, preventing further infection from the cell.


The metabolic process of autophagy is an important regulator of cellular life and death. When the cell undergoes stress or nutrient deprivation, damaged organelles or proteins are degraded into basic components to be recycled. This catabolic process has been shown to play an important role in a variety of human diseases such as cancer, neurodegenerative diseases, and diabetes. Another disease autophagy could potentially play a part in is COVID-19, a respiratory disease caused by the virus SARS-CoV-2.
Exploring the effect of autophagy in COVID-19 further could potentially lead to novel therapeutics for COVID-19. One possibility to prevent the spread of the virus is activating autophagy to degrade the Ace2 receptor. Breaking down the Ace2 receptor prevents the virus from infecting cells. Autophagy could also be useful in decreasing viral replication by degrading viral particle components such as the spike proteins to prevent the formation of new coronaviruses inside host cells. Another potential way autophagy can play a role in COVID-19 is by degrading ribosomes, which cells use to translate their proteins to form new viruses and infect other cells. By breaking down ribosomes, the virus will have no way of replicating itself, preventing it from spreading to the rest of the body.
One problem with these potential therapeutic strategies is that activating autophagy could have side effects. For example, because autophagy is a stress-induced response, it may help keep infected cells alive, which would further promote viral spread. Another problem that researchers could encounter is the virus de-acidifying the lysosome, an important organelle used in autophagy. Researchers may need to identify ways to re-acidify lysosomes to restore normal functions in infected cells to use autophagy to fight COVID-19.
In order to test how autophagy can be used to treat COVID-19, aziythromicine, an FDA-approved drug, could potentially act as an autophagy activator. Rapamycin, an mTOR inhibitor that is in phase 3 trials, is another possible drug that could be expedited to use as an autophagy activator.
Political policy plays an important role in healthcare policy by providing funding for further research. Due to how COVID-19 has now plagued our world, therapeutic research for COVID is of high priority. However, it is possible that if more funding had been given to research SARS-CoV or MERS-CoV before, this pandemic could have been prevented or been under control in a shorter period of time.
Researching the potential of using autophagy to treat COVID-19 could help prevent widespread infections by future novel coronaviruses and thereby prevent coronavirus pandemics in the future. Additionally, testing how activating autophagy affects coronavirus will significantly improve our ability to design therapeutics for other viral infections.


  1. Sarbari Saha et al., “Autophagy in Health and Disease: A Comprehensive Review,” Biomedicine & Pharmacotherapy 104 (August 2018): 485–95,
  2. Lorenzo Galluzzi et al., “Molecular Definitions of Autophagy and Related Processes,” The EMBO Journal 36, no. 13 (July 3, 2017): 1811–36,
  3. Oxford Dictionary of Biochemistry and Molecular Biology, Oxford Dictionary of Biochemistry and Molecular Biology (Oxford University Press, 2006),
  4. Wen-wen Li, Jian Li, and Jin-ku Bao, “Microautophagy: Lesser-Known Self-Eating,” Cellular and Molecular Life Sciences 69, no. 7 (April 1, 2012): 1125–36,
  5. “Chaperone-Mediated Autophagy – an Overview | ScienceDirect Topics,” accessed October 24, 2020,
  6. Yuchen Feng et al., “The Machinery of Macroautophagy,” Cell Research 24, no. 1 (January 2014): 24–41,
  7. Jason D. Plummer and Jay E. Johnson, “Extension of Cellular Lifespan by Methionine Restriction Involves Alterations in Central Carbon Metabolism and Is Mitophagy-Dependent,” Frontiers in Cell and Developmental Biology 7 (2019),
  8. “The Cell’s Dilemma, or the Story of Cell Death: An Entertainment in Three Acts – Green – 2016 – The FEBS Journal – Wiley Online Library,” accessed October 24, 2020,
  9. Fesler, “Autophagy Regulated by MiRNAs in Colorectal Cancer Progression and Resistance,” accessed October 25, 2020,;year=2017;volume=3;issue=3;spage=96;epage=100;aulast=Fesler.
  10. “Phosphorylation – an Overview | ScienceDirect Topics,” accessed October 24, 2020,
  11. Donna Denton and Sharad Kumar, “Autophagy-Dependent Cell Death,” Cell Death & Differentiation 26, no. 4 (April 2019): 605–16,
  12. Johnna Doherty and Eric H. Baehrecke, “Life, Death and Autophagy,” Nature Cell Biology 20, no. 10 (October 2018): 1110–17,
  13. The Walter and Eliza Hall Institute of Medical Research, “Cell Death,” Text, WEHI (The Walter and Eliza Hall Institute of Medical Research, November 11, 2014),
  14. Nicholas S. Tolwinski, “Introduction: Drosophila—A Model System for Developmental Biology,” Journal of Developmental Biology 5, no. 3 (September 20, 2017),
  15. Kathryn Ray et al., “Growth and Differentiation of the Larval Mosquito Midgut,” Journal of Insect Science 9 (July 15, 2009),
  16. Satoko Arakawa et al., “Role of Atg5-Dependent Cell Death in the Embryonic Development of Bax/Bak Double-Knockout Mice,” Cell Death and Differentiation 24, no. 9 (September 2017): 1598–1608,
  17. Ioannis P. Nezis et al., “Autophagic Degradation of DBruce Controls DNA Fragmentation in Nurse Cells during Late Drosophila Melanogaster Oogenesis,” Journal of Cell Biology 190, no. 4 (August 23, 2010): 523–31,
  18. Ian G. Ganley et al., “ULK1·ATG13·FIP200 Complex Mediates MTOR Signaling and Is Essential for Autophagy,” Journal of Biological Chemistry 284, no. 18 (May 1, 2009): 12297–305,
  19. Manoj B. Menon and Sonam Dhamija, “Beclin 1 Phosphorylation – at the Center of Autophagy Regulation,” Frontiers in Cell and Developmental Biology 6 (2018),
  20. “Phospholipids | Introduction to Chemistry,” accessed December 1, 2020,
  21. “Targeting Autophagy in Cancer – Onorati – 2018 – Cancer – Wiley Online Library,” accessed December 1, 2020,
  22. Hayato Hikita, Sadatsugu Sakane, and Tetsuo Takehara, “Mechanisms of the Autophagosome-Lysosome Fusion Step and Its Relation to Non-Alcoholic Fatty Liver Disease,” Liver Research 2, no. 3 (September 1, 2018): 120–24,
  23. “SNARE,” Oxford Reference, accessed October 24, 2020,
  24. Naidi Yang and Han-Ming Shen, “Targeting the Endocytic Pathway and Autophagy Process as a Novel Therapeutic Strategy in COVID-19,” International Journal of Biological Sciences 16, no. 10 (March 15, 2020): 1724–31,
  25. Xian-Yong Zhou et al., “Inhibition of Autophagy Blocks Cathepsins–TBid–Mitochondrial Apoptotic Signaling Pathway via Stabilization of Lysosomal Membrane in Ischemic Astrocytes,” Cell Death & Disease 8, no. 2 (February 2017): e2618–e2618,
  26. “WIPI Proteins: Essential PtdIns3P Effectors at the Nascent Autophagosome | Journal of Cell Science,” accessed December 1, 2020,
  27. Young Chul Kim and Kun-Liang Guan, “MTOR: A Pharmacologic Target for Autophagy Regulation,” The Journal of Clinical Investigation 125, no. 1 (January 2, 2015): 25–32,
  28. Christian A. Devaux et al., “New Insights on the Antiviral Effects of Chloroquine against Coronavirus: What to Expect for COVID-19?,” International Journal of Antimicrobial Agents 55, no. 5 (May 2020): 105938,
  29. Kaipeng Jing and Kyu Lim, “Why Is Autophagy Important in Human Diseases?,” Experimental & Molecular Medicine 44, no. 2 (February 2012): 69–72,
  30. Chun-Lei Cheng et al., “Role of Insulin/Insulin-like Growth Factor 1 Signaling Pathway in Longevity,” World Journal of Gastroenterology 11, no. 13 (April 7, 2005): 1891–95,
  31. Joseph M. Schinaman et al., “Rapamycin Modulates Tissue Aging and Lifespan Independently of the Gut Microbiota in Drosophila,” Scientific Reports 9, no. 1 (May 24, 2019): 7824,
  32. David E. Harrison et al., “Rapamycin Fed Late in Life Extends Lifespan in Genetically Heterogeneous Mice,” Nature 460, no. 7253 (July 2009): 392–95,
  33. Ivana Bjedov et al., “Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila Melanogaster,” Cell Metabolism 11, no. 1 (January 6, 2010): 35–46,
  34. Ling Yang et al., “Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin Resistance,” Cell Metabolism 11, no. 6 (June 9, 2010): 467–78,
  35. Rashed Abdullah et al., “Parkinson’s Disease and Age: The Obvious but Largely Unexplored Link,” Experimental Gerontology, Proceedings of the Twelfth International Symposium on the Neurobiology and Neuroendocrinology of Aging, Bregenz, Austria July 27–August 1, 2014, 68 (August 1, 2015): 33–38,
  36. Antonella Caccamo et al., “Molecular Interplay between Mammalian Target of Rapamycin (MTOR), Amyloid-Beta, and Tau: Effects on Cognitive Impairments,” The Journal of Biological Chemistry 285, no. 17 (April 23, 2010): 13107–20,
  37. Brinda Ravikumar et al., “Inhibition of MTOR Induces Autophagy and Reduces Toxicity of Polyglutamine Expansions in Fly and Mouse Models of Huntington Disease,” Nature Genetics 36, no. 6 (June 2004): 585–95,
  38. Yi-Chi Wu, Ching-Sung Chen, and Yu-Jiun Chan, “The Outbreak of COVID-19: An Overview,” Journal of the Chinese Medical Association 83, no. 3 (March 2020): 217–20,
  39. Marco Ciotti et al., “COVID-19 Outbreak: An Overview,” Chemotherapy 64, no. 5–6 (April 7, 2020): 215–23,
  40. Anthony R. Fehr and Stanley Perlman, “Coronaviruses: An Overview of Their Replication and Pathogenesis,” Coronaviruses 1282 (February 12, 2015): 1–23,
  41. “Characterization of the Budding Compartment of Mouse Hepatitis Virus: Evidence That Transport from the RER to the Golgi Complex Requires Only One Vesicular Transport Step,” The Journal of Cell Biology 124, no. 1 (January 1, 1994): 55–70.
  42. Dewald Schoeman and Burtram C. Fielding, “Coronavirus Envelope Protein: Current Knowledge,” Virology Journal 16, no. 1 (May 27, 2019): 69,
  43. Tiffany Tang et al., “Coronavirus Membrane Fusion Mechanism Offers a Potential Target for Antiviral Development,” Antiviral Research 178 (June 2020): 104792,
  44. Sourish Ghosh et al., “β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway,” Cell 183, no. 6 (December 2020): 1520-1535.e14,
  45. Jared S. Hopkins, “Pfizer’s Covid-19 Vaccine Proves 90% Effective in Latest Trials,” Wall Street Journal, November 9, 2020, sec. Business,
  46. “Unveiling How Coronavirus Hijacks Our Cells to Help Rush New Drugs to Patients,” Unveiling How Coronavirus Hijacks Our Cells to Help Rush New Drugs to Patients | UC San Francisco, accessed December 1, 2020,
  47. Nils C. Gassen et al., “SKP2 Attenuates Autophagy through Beclin1-Ubiquitination and Its Inhibition Reduces MERS-Coronavirus Infection,” Nature Communications 10, no. 1 (December 18, 2019): 2,
  48. Dr Kausik Majumdar says, “Autophagy Process: The Key to Effective MERS-Coronavirus Treatment?,” Drug Target Review (blog), accessed November 8, 2020,
  49. Alain Calender et al., “Modeling Potential Autophagy Pathways in COVID-19 and Sarcoidosis,” Trends in Immunology 41, no. 10 (October 1, 2020): 856–59,

About the Author

Tanvi is from California, USA and will attend UC Berkeley in the fall of 2021. She is interested in pursuing pre-med at college, and her dream would be to become an OBGYN. She has volunteered at hospitals and participated in surgical internships. With the recent global pandemic, she was interested in researching a potential therapeutic for COVID-19.

1 thought on “Autophagy: A Multipotentialite”

Leave a Comment

Your email address will not be published. Required fields are marked *