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Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Open accessAbstract
Autophagy is a major catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles. This pathway is activated under environmental stress conditions, during development and in various pathological situations. In this study, we describe the role of reactive oxygen species (ROS) as signaling molecules in starvation-induced autophagy. We show that starvation stimulates formation of ROS, specifically H(2)O(2). These oxidative conditions are essential for autophagy, as treatment with antioxidative agents abolished the formation of autophagosomes and the consequent degradation of proteins. Furthermore, we identify the cysteine protease HsAtg4 as a direct target for oxidation by H(2)O(2), and specify a cysteine residue located near the HsAtg4 catalytic site as a critical for this regulation. Expression of this regulatory mutant prevented the formation of autophagosomes in cells, thus providing a molecular mechanism for redox regulation of the autophagic process.
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“Induction of autophagy following nutrient starvation requires the production of hydrogen peroxide that oxidizes autophagy‐related (ATG)4.”
From Reactive Oxygen Species in Cancer: Current Findings and Future Directions (2021) · cites this paper as [51]
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“MTOR suppression does not always induce autophagy, such as when BECN1 undergoes inhibitory phosphorylation by the growth factor signaling molecules EGFR and AKT, when microglia are activated by lipopolysaccharide (LPS), a TLR4 ligand [766], or during Salmonella infection [767-769].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [767]
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1 retracted
Mariño, G., Urı́a, J. A., Puente, X. S., Quesada, V., Bordallo, J., & López-Otı́n, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208247200 · Cited by 206
RetractedRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
Autophagy in Health and Disease: A Double-Edged Sword
Shintani, T., & Klionsky, D. J. (2004) · Science · doi:10.1126/science.1099993 · Cited by 2,559
A ubiquitin-like system mediates protein lipidation
Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., et al. (2000) · Nature · doi:10.1038/35044114 · Cited by 2,139
LC3 conjugation system in mammalian autophagy
Tanida, I., Ueno, T., & Kominami, E. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.05.009 · Cited by 1,512
WWW-query: An on-line retrieval system for biological sequence banks
Perrière, G., & Gouy, M. (1996) · Biochimie · doi:10.1016/0300-9084(96)84768-7 · Cited by 1,488
LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation
Kabeya, Y., Mizushima, N., Yamamoto, A., Oshitani-Okamoto, S., Ohsumi, Y., & Yoshimori, T. (2004) · Journal of Cell Science · doi:10.1242/jcs.01131 · Cited by 1,394
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BackgroundDesideri, E., Vegliante, R., Cardaci, S., Nepravishta, R., Paci, M., & Ciriolo, M. R. (2014) · Autophagy · doi:10.4161/auto.29456 · Cited by 70
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Autophagy in cigarette smoke-induced chronic obstructive pulmonary disease
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“Although ROS have been shown to be required for autophagy induction, it has been proposed that decreased ROS levels might also be necessary to allow the activation of Atg4 and ATG4B in order to release members of the Atg8 protein family from autophagosomal membranes (PérezPérez et al., 2014; Scherz-Shouval et al., 200…”
BackgroundInfluentialHyttinen, J. M. T., Błasiak, J., Niittykoski, M., Kinnunen, K., Kauppinen, A., Salminen, A., & Kaarniranta, K. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.03.006 · Cited by 73
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Sung, H. K., Song, E., Jahng, J. W. S., Pantopoulos, K., & Sweeney, G. (2019) · Scientific Reports · doi:10.1038/s41598-019-41111-6 · Cited by 70
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Liu, K., Guo, C. W., Lao, Y., Yang, J., Chen, F., Zhao, Y., Yang, Y. A., Yang, J., & Yi, J. (2019) · Autophagy · doi:10.1080/15548627.2019.1647944 · Cited by 72
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BackgroundMethodInfluentialSulforaphane induces autophagy through ERK activation in neuronal cells
Jo, C., Kim, S., Cho, S., Choi, K. J., Yun, S., Koh, Y. H., Johnson, G. V. W., & Park, S. I. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.06.036 · Cited by 69
“ROS can also act as signals for the activation of autophagy [18–21].”
BackgroundCell type-dependent ROS and mitophagy response leads to apoptosis or necroptosis in neuroblastoma
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Agrotis, A., von Chamier, L., Oliver, H., Kiso, K., Singh, T., & Ketteler, R. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ac119.009977 · Cited by 69
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Lee, J. H., Parveen, A., Do, M. H., Kang, M. C., Yumnam, S., & Kim, S. Y. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-2602-1 · Cited by 69
Huang, C., Yan, S., & Zhang, Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00219-w · Cited by 75
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
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Lettieri‐Barbato, D., Aquilano, K., Baldelli, S., Cannata, S. M., Bernardini, S., Rotilio, G., & Ciriolo, M. R. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.137 · Cited by 70
Zhang, L., Guo, M., Li, J., Zheng, Y., Zhang, S., Xie, T., & Liu, B. (2015) · Molecular BioSystems · doi:10.1039/c5mb00466g · Cited by 71
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ResultKumar, D., Das, B., Sen, R., Kundu, P., Manna, A., Sarkar, A., Chowdhury, C., Chatterjee, M., & Das, P. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139657 · Cited by 68
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BackgroundLi, X., Cui, X., Chen, Y., Wu, T., Xu, H., Yin, H., & Wu, Y. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00121 · Cited by 70
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Rang, F. J., & Boonstra, J. (2014) · Biology · doi:10.3390/biology3020403 · Cited by 65
“progenitor cells [70], and autophagy [71,72].”
Huang, C., Chen, K.-L., Cheung, C. H. A., & Chang, J. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.020 · Cited by 69
Pérez‐Pérez, M. E., Lemaire, S. D., & Crespo, J. L. (2016) · PLANT PHYSIOLOGY · doi:10.1104/pp.16.01582 · Cited by 69
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Narni-Mancinelli, É., Soudja, S. M., Crozat, K., Dalod, M., Gounon, P., Geissmann, F., & Lauvau, G. S. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002457 · Cited by 66
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Xu, J., Wu, Y., Lu, G. X., Xie, S., Ma, Z., Chen, Z., Shen, H., & Xia, D. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.017 · Cited by 67
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BackgroundCampanella, M., Seraphim, A., Abeti, R., Casswell, E. J., Echave, P., & Duchen, M. R. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.02.023 · Cited by 67
Tyagi, N., Vacek, J. C., Givvimani, S., Sen, U., & Tyagi, S. C. (2010) · Journal of Receptors and Signal Transduction · doi:10.3109/10799891003614808 · Cited by 65
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BackgroundInfluentialVasko, R. (2016) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6666 · Cited by 69
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The role of NADPH oxidases in neuronal development
Terzi, A., & Suter, D. M. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.04.027 · Cited by 68
DHA-induced stress response in human colon cancer cells – Focus on oxidative stress and autophagy
Pettersen, K., Monsen, V. T., Pettersen, C. H. H., Overland, H. B., Pettersen, G. K., Samdal, H., Tesfahun, A. N., Lundemo, A. G., Bjørkøy, G., & Schønberg, S. A. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.11.018 · Cited by 68
“ROS have also been suggested to induce autophagy by directly controlling the enzymatic activity of ATG4 needed for maturation of LC3-family members and formation of LC3B-II-positive autophagosomes [18].”
BackgroundLi, X., Wang, M., Li, S., Chen, Y., Wang, M., Wu, Z., Sun, X., Yao, L., Dong, H., Song, Y., et al. (2021) · Theranostics · doi:10.7150/thno.57804 · Cited by 66
“At normal cellular levels, ROS regulate a wide range of cellular responses, including growth, differentiation, ageing, transcription factor activity, and inflammatory reactions [41-47].”
BackgroundPEX13 prevents pexophagy by regulating ubiquitinated PEX5 and peroxisomal ROS
Demers, N. D., Riccio, V., Jo, D. S., Bhandari, S., Law, K. B., Liao, W., Kim, C., McQuibban, G. A., Choe, S., Cho, D., et al. (2022) · Autophagy · doi:10.1080/15548627.2022.2160566 · Cited by 65
“Increases in cellular hydrogen peroxide (H2O2) induce autophagy [53,54], and given that CAT is the major peroxisomal antioxidant [55], we examined whether the loss of either PEX13 or PEX1 induces oxidative stress.”
BackgroundChoi, S., Kim, B.-Y., Dadakhujaev, S., Oh, J.-Y., Kim, T., Kim, J. Y., & Kim, E. K. (2012) · Autophagy · doi:10.4161/auto.22067 · Cited by 65
Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells
Poornima, P., Velmurugan, B. K., Weng, C., & Padma, V. V. (2014) · Food and Chemical Toxicology · doi:10.1016/j.fct.2014.03.008 · Cited by 65
“ROS are known to be signaling molecules in apoptotic cell death (Scherz-Shouval et al., 2007).”
BackgroundOjha, R., Jha, V., Singh, S. K., & Bhattacharyya, S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.07.007 · Cited by 68
Autophagy as an important process in gut homeostasis and Crohn’s disease pathogenesis
Xavier, R. J., Huett, A. S., & Rioux, J. D. (2008) · Gut · doi:10.1136/gut.2007.134254 · Cited by 67
Zhao, Y., Huang, G., Chen, S., Gou, Y., Dong, Z., & Zhang, X. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17081196 · Cited by 65
Huang, Y.-N., Yang, L.-Y., Greig, N. H., Wang, Y.-C., Lai, C.-C., & Wang, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-19654-x · Cited by 64
Das, C. K., Banerjee, I., & Mandal, M. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.08.020 · Cited by 70
Autophagy in neonatal hypoxia ischemic brain is associated with oxidative stress
Lü, Q., Harris, V. A., Kumar, S., Mansour, H. M., & Black, S. M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.06.016 · Cited by 65
“Previous studies have demonstrated that ROS, especially H2O2, are essential for autophagy [43].”
BackgroundHeat shock increases levels of reactive oxygen species, autophagy and apoptosis
Kassis, S., Grondin, M., & Averill‐Bates, D. A. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118924 · Cited by 71
Gonzalez, Y., Aryal, B., Chehab, L., & Rao, V. A. (2014) · Oncotarget · doi:10.18632/oncotarget.1715 · Cited by 60
“Previous studies have shown that ROS stimulates autophagy by modifying autophagy related proteins [40, 41].”
BackgroundGlioblastoma stem cells resistant to temozolomide-induced autophagy.
Fu, J., Liu, Z.-G., Liu, X., Chen, F., Hong-liu, S., Pangjesse, C.-S., Ng, H., & Chen, Z. (2009) · PubMed · doi:10.3760/cma.j.issn.0366-6999.2009.11.004 · Cited by 64
“Autophagy machinery can be activated by various agents such as DNA damages,(11) disruption of PI3K/AKT/mTOR signaling,(12) deprivation of nutrients or amino acids,(13) and oxidative stress.(14,15) The components of the molecular machinery responsible for autophagy are products of the autophagy-related (Atg) genes.”
BackgroundCi, Y., Shi, K., An, J., Yang, Y., Hui, K., Wu, P., Shi, L., & Xu, C. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.506 · Cited by 64
“Additionally, mitochondrial ROSare critical for autophagy.(31) It is generally accepted that ROS induce autophagy and that this process is mediated by various signalling cascades.”
BackgroundMnSOD Upregulation Induces Autophagic Programmed Cell Death in Senescent Keratinocytes
Deruy, E., Gosselin, K., Vercamer, C., Martien, S., Bouali, F., Slomianny, C., Bertout, J., Bernard, D., Pourtier, A., & Abbadie, C. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012712 · Cited by 67
“In consequence to these oxidative damages, and potentially through the oxidation of Atg4 by H2O2, autophagy is highly activated and progressively eliminates all the oxidized vital cell components, leading to cell death.”
BackgroundReactive Oxygen Species Regulate Autophagy through Redox-Sensitive Proteases
Liu, Z., & Lenardo, M. J. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.03.016 · Cited by 48
“Scherz-Shouval et al. (2007) report that ROS inactivate HsAtg4A which causes the accumulation of Atg8-PE.”
BackgroundAutophagy as a Possible Underlying Mechanism of Nanomaterial Toxicity
Cohignac, V., Landry, M., Boczkowski, J., & Lanone, S. (2014) · Nanomaterials · doi:10.3390/nano4030548 · Cited by 70
“In these studies, it has been shown that H2O2 induces autophagy via an inactivation of Atg4 at the site of autophagosomes formation, thus allowing the conversion of LC3-I to LC3-II, which, as mentioned before, is crucial for the initial steps of autophagy [163].”
BackgroundROS dependent copper toxicity in Hydra -biochemical and molecular study
Zeeshan, M., Anbazhagan, M., Ghaskadbi, S., Ramaswamy, B. R., & Akbarsha, M. A. (2016) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2016.02.008 · Cited by 65
Laureano‐Marín, A. M., Moreno, I., Romero, L. C., & Gotor, C. (2016) · PLANT PHYSIOLOGY · doi:10.1104/pp.16.00110 · Cited by 64
“Moreover, redox regulation of 481 cysteine protease ATG4 has been characterized in detail in mammalian systems, and a 482 cysteine residue located near the catalytic site has been found to be critical for this regulation 483 (Scherz-Shouval et al., 2007).”
BackgroundGlutathione and glutathione derivatives in immunotherapy
Fraternale, A., Brundu, S., & Magnani, M. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0202 · Cited by 64
Urano, Y., Mori, C., Fuji, A., Konno, K., Yamamoto, T., Yashirogi, S., Ando, M., Saito, Y., & Noguchi, N. (2018) · Autophagy · doi:10.1080/15548627.2018.1493043 · Cited by 64
“It has been reported that oxidation of Atg4 at cysteine inactivates its delipidating activity on LC3, thereby leading to the induction of autophagosome formation [52].”
BackgroundKouroumalis, E., Voumvouraki, A., Augoustaki, A., & Samonakis, D. N. (2021) · World Journal of Hepatology · doi:10.4254/wjh.v13.i1.6 · Cited by 66
Activation of PPARα enhances astroglial uptake and degradation of β-amyloid
Raha, S., Ghosh, A., Dutta, D., Patel, D. R., & Pahan, K. (2021) · Science Signaling · doi:10.1126/scisignal.abg4747 · Cited by 63
“LC3-II remains bound to the autophagosome membrane and is essential for the de novo production of autophagic vacuole (36, 37).”
ArulJothi, K. N., Kumaran, K., Senthil, S., Nidhu, A. B., Munaff, N., Babu, J. V., Kirubakaran, R., Singh, S. K., Gupt, G., Dua, K., et al. (2022) · Medical Oncology · doi:10.1007/s12032-022-01900-y · Cited by 67
Ni, C., Yu, C., Lu, H., Yang, J., Huang, H., Chen, P., Wu, S., Ip, S., Chiang, S., Lin, J., et al. (2012) · Environmental Toxicology · doi:10.1002/tox.21801 · Cited by 63
“The previous study demonstrated that ROS has been shown to activate autophagy through autophagy-related 4 (Scherz-Shouval et al., 2007).”
BackgroundHigh-Throughput Fluorescence Assay for Small-Molecule Inhibitors of Autophagins/Atg4
Shu, C., Madiraju, C., Zhai, D., Welsh, K., Diaz, P. W., Sergienko, E. A., Sano, R., & Reed, J. C. (2011) · SLAS DISCOVERY · doi:10.1177/1087057110392996 · Cited by 63
Thayyullathil, F., Rahman, A. U., Pallichankandy, S., Patel, M. C., & Galadari, S. (2014) · FEBS Open Bio · doi:10.1016/j.fob.2014.08.005 · Cited by 64
“Recently, several reports provided strong evidence for the involvement of ROS in the induction of autophagy in response to chemotherapy-induced stress [9,10].”
BackgroundInfluentialRole of gut microbiota in Crohn’s disease
Baker, P., Love, D. R., & Ferguson, L. R. (2009) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.09.47 · Cited by 63
Metadata
- Authors
- Scherz‐Shouval, R., Shvets, E., Fass, E., Shorer, H., Gil, L., & Elazar, Z.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Elazar, Zvulun
- Venue
- The EMBO Journal
- Published
- 2007-03-08
- Volume
- 26
- Issue
- 7
- Pages
- 1749-1760
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC6517991
- OpenAlex
- W2114806766
- Cited by
- 2,101
- References
- 51
- Citations by year
- 2026: 38 · 2025: 60 · 2024: 77 · 2023: 86 · 2022: 115 · 2021: 141 · 2020: 137 · 2019: 108 · 2018: 122 · 2017: 136 · 2016: 118 · 2015: 132 · 2014: 170 · 2013: 140 · 2012: 146
- FWCI
- 59.86
- Type
- journal article
- Language
- en
- Update notices
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- reactive oxygen species, autophagy, ATG4, hydrogen peroxide, starvation, redox regulation, cysteine protease, autophagosome formation, oxidative stress signaling, protein degradation
- MeSH terms
- Autophagy-Related Proteins, Amino Acid Sequence, Animals, Autophagy, Cricetulus, Cysteine, Cysteine Endopeptidases, Enzyme Activation, Food Deprivation, Cricetinae, HeLa Cells, Humans, Models, Biological, Molecular Sequence Data, Mutation, Oxidation-Reduction, Phylogeny, CHO Cells, Reactive Oxygen Species, Phosphatidylinositol 3-Kinases, Mice
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