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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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BackgroundAutophagy drives fibroblast senescence through MTORC2 regulation
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Pajares, M., Jiménez-Moreno, N., Dias, I. H. K., BÜTÜNER, B. D., Vučetić, M., Fladmark, K. E., Başağa, H., Ribarič, S., Milisav, I., & Cuadrado, A. (2015) · Redox Biology · doi:10.1016/j.redox.2015.07.003 · Cited by 177
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Self-citationSulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress
Li, D., Shao, R., Wang, N., Zhou, N., Du, K., Shi, J., Wang, Y., Zhao, Z., Ye, X., Zhang, X., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1739442 · Cited by 177
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Venditti, P., & Meo, S. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062173 · Cited by 176
Marino, M. L., Fais, S., Djavaheri‐Mergny, M., Villa, A., Meschini, S., Lozupone, F., Venturi, G., Mina, P. D., Pattingre, S., Rivoltini, L., et al. (2010) · Cell Death and Disease · doi:10.1038/cddis.2010.67 · Cited by 172
“It is known that ROS are involved in the autophagic response of cancer cells to nutrient starvation or metabolic stress.(26) Moreover, PPIs have been reported to cause alkalinization of lysosomal pH (Supplementary Figure 1b) and disturbance of acidic vesicle traffic.”
BackgroundAutophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration
Kaarniranta, K., Tokarz, P., Koskela, A. K. J., Paterno, J. J., & Błasiak, J. (2016) · Cell Biology and Toxicology · doi:10.1007/s10565-016-9371-8 · Cited by 176
“Moreover, some data suggest that mitochondria are the main source of ROS needed for the induction of autophagy (Scherz-Shouval et al. 2007a; Scherz-Shouval et al. 2007b) (reviewed in ScherzShouval and Elazar (2007)).”
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Duchen, M. R., & Szabadkai, G. (2010) · Essays in Biochemistry · doi:10.1042/bse0470115 · Cited by 171
Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management
Dinić, S., Јovanović, J. A., Uskoković, A. S., Mihailović, M., Grdović, N., Tolić, A., Rajić, J., Đorđević, M., & Vidaković, M. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1006376 · Cited by 196
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“In addition, starvation-induced H2O2 oxidizes ATG4 at Cys78 to spatiotemporally inactivate ATG4 and ensure that lipidated LC3-II can facilitate autophagosome formation before deconjugation [67].”
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“Recently, reactive oxygen species were found to be essential for starvation-induced autophagy to proceed (”
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Fu, J., Shao, C.-J., Chen, F.-R., Ng, H., & Chen, Z. (2009) · Neuro-Oncology · doi:10.1093/neuonc/nop005 · Cited by 167
“However, is the regulation of autophagy limited to mitochondria ROS production alone? Scherz-Shouval et al.(26) discovered redox as a posttranslational modification that regulates autophagy through the regulation of autophagy effector Atg4.”
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Gao, Q. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-15-0602-4_9 · Cited by 167
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Gogvadze, V. G., Orrenius, S., & Zhivotovsky, B. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.11.007 · Cited by 165
“A target for H2O2 was the cysteine protease HsAtg4, particuarly, a cysteine residue located near the HsAtg4 catalytic site [40].”
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Peroxisome Metabolism and Cellular Aging
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“Moreover, hydrogen peroxide serves as a potent signaling molecule that initiates autophagy through redox-sensitive proteases (61).”
BackgroundHow does the macula protect itself from oxidative stress?
Handa, J. T. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.03.006 · Cited by 154
“A wide range of specific cellular responses relevant to AMD are signaled through ROS, such as feedback regulation after excess metabolism (Brunelle et al., 2005; Guzy et al., 2005), hypoxia via hypoxia inducible factor 1 (Guzy et al., 2005), regulation of autophagy through ATF4 (Scherz-Shouval et al., 2007), and regul…”
BackgroundCurrent Challenges and Opportunities of Photodynamic Therapy against Cancer
Huis in ‘t Veld, R. V., Heuts, J., Ma, S., Cruz, L. J., Ossendorp, F. A., & Jager, M. J. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020330 · Cited by 159
The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes
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“Atg8 lipidation is a crucial step for dynamic membrane rearrangement during autophagosome formation and therefore, this process is well controlled by multiple autophagic factors (Meijer and Codogno, 2006; Ohsumi, 2001; Scherz-Shouval et al., 2007).”
BackgroundSelf-citationZuo, W., Zhang, S., Xia, C., Guo, X., He, W., & Chen, N. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.07.002 · Cited by 158
“Nonselective autophagy and mitophagy have been shown to be triggered in response to nutrition deprivation, starvation or rapamycin (Lee et al., 2012; Scherz-Shouval et al., 2007; S€oren M et al., 2012).”
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Antioxidants Targeting Mitochondrial Oxidative Stress: Promising Neuroprotectants for Epilepsy
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Wang, X., Fan, D., Cao, X., Ye, Q., Wang, Q., Zhang, M., & Xiao, C. (2022) · Antioxidants · doi:10.3390/antiox11061153 · Cited by 176
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BackgroundRegulation of autophagy by protein post-translational modification
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BackgroundInfluentialMolecular basis of mycobacterial survival in macrophages
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“Members of the Atg family include Atg4s that act both as conjugating and de-conjugating enzymes with activities of cysteine proteases (116, 324).”
Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells
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“After autophagosomes mature and fuse with lysosomes, the local environment changes to H 2 O 2 − deficiency, where ATG4 turns to an active state, and thus LC3 is delipidated and recycles once again.(68) ATG4 exists in the CNS, and so oxidative stress may influence the activity of ATG4 and induce autophagy.”
BackgroundRoles of reactive oxygen species in cell signaling pathways and immune responses to viral infections
Li, Z., Xu, X., Leng, X., He, M., Wang, J., Cheng, S., & Wu, H. (2016) · Archives of Virology · doi:10.1007/s00705-016-3130-2 · Cited by 154
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BackgroundmTORC1 pathway in DNA damage response
Ma, Y., Vassetzky, Y. S., & Dokudovskaya, S. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.06.011 · Cited by 157
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“Autophagy occurs at basal levels to degrade long-lived cytosolic proteins and organelles but is also upregulated to promote cell survival in response to nutrient starvation (10) and other cellular stresses including radiation (11), chemotherapy (12), and oxidative stress (13).”
Unraveling the Truth About Antioxidants: ROS and disease: finding the right balance
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“The relevance of ROS functioning, as signaling molecules in autophagy regulation, has been suggested in the context of the vitamin D-cathelicidin axis during infection and inflammation; 1,25D3 leads to significant ROS production, which promotes autophagy (70) and antimicrobial activity (71).”
BackgroundHypoxia-activated autophagy accelerates degradation of SQSTM1/p62
Pursiheimo, J.-P., Rantanen, K., Heikkinen, P. T., Johansen, T., & Jaakkola, P. (2008) · Oncogene · doi:10.1038/onc.2008.392 · Cited by 155
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“In addition, increasing evidence shows an association between ROS generation and the initiation of autophagy.(5,6,21) Several reports have indicated that compound K provokes apoptosis in colon cancer cells.”
BackgroundOxidative Stress and Autophagy in the Regulation of Lysosome-Dependent Neuron Death
Pivtoraiko, V. N., Stone, S. L., Roth, K. A., & Shacka, J. J. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2263 · Cited by 154
“Along these lines, ROS induced by starvation were found recently to regulate macroautophagy induction critically through the cys-teine-dependent activity of Atg4, an autophagy-specific protein that regulates autophagosome formation (124).”
Ins(1,4,5) P 3 receptor-mediated Ca 2+ signaling and autophagy induction are interrelated
Decuypere, J.-P., Welkenhuyzen, K., Luyten, T., Ponsaerts, R., Dewaele, M., Molgó, J., Agostinis, P., Missiaen, L., De Smedt, H., Parys, J. B., et al. (2011) · Autophagy · doi:10.4161/auto.7.12.17909 · Cited by 159
ATM‐CHK2‐Beclin 1 axis promotes autophagy to maintain ROS homeostasis under oxidative stress
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Glutaminolysis and autophagy in cancer
Villar, V. H., Merhi, F., Djavaheri-Mergny, M., & Durán, R. V. (2015) · Autophagy · doi:10.1080/15548627.2015.1053680 · Cited by 143
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“Specific examples include regulation of protein tyrosine phosphatases (63), PTEN (40), and hypoxia-inducible factor (HIF-1a) (4, 30, 45), circadian rhythms (18), as well as regulation of autophagy (64) and inflammatory responses (5, 52).”
BackgroundRecent Insights into the Mitochondrial Role in Autophagy and Its Regulation by Oxidative Stress
Agujetas, V. R., de Dios, C., Pinilla, L. L., Marı́, M., Morales, A., & Colell, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3809308 · Cited by 153
“The lipidation of MAP1LC3/LC3 homologs is indispensable to normal development of the isolation membrane during the closing step, thereby when overexpression of an ATG4 dominant-negative mutant is used (particularly ATG4B), it results in the accumulation of unclosed isolation membranes [81].”
BackgroundInfluentialGao, M., Yeh, P.-Y., Lu, Y., Hsu, C., Chen, K., Lee, W.-C., Feng, W.-C., Chen, C., Kuo, M., & Cheng, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1642 · Cited by 147
“Moreover, ROS are essential for autophagosome formation under starvation conditions through targeting cysteine protease HsAtg 4 ,a n autophagy-related gene, leading to cell survival ( 14 ).”
BackgroundAutophagy Suppresses Age-Dependent Ischemia and Reperfusion Injury in Livers of Mice
Wang, J., Ahn, I., Fischer, T. D., Byeon, J. I., Dunn, W. A., Behrns, K. E., Leeuwenburgh, C., & Kim, J. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.08.005 · Cited by 146
Immunologic manifestations of autophagy
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“Moreover, increasing pools of depolarized mitochondria resulting from the absence of autophagy contribute ROS, further enhancing RLR outputs (42).”
A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B
Pengo, N., Agrotis, A., Prak, K., Jones, J., & Ketteler, R. (2017) · Nature Communications · doi:10.1038/s41467-017-00303-2 · Cited by 148
“All PCR were performed at 30 cycles using either Pyrobest DNA polymerase (Takara, R005A) (For pGEXATG4BC74S, pGEXATG4BS316A, pGEX GST-ULK1cd and pET LC3-GST) or Phusion polymerase (New England Biolabs, M0530S). pDONR223 ATG4B was created by recombining ATG4B amplified by PCR from pHTN-HaloTag-ATG4B with pDONR223 and t…”
BackgroundInfluentialRedox Regulation of Homeostasis and Proteostasis in Peroxisomes
Walker, C. L., Pomatto, L. C. D., Tripathi, D. N., & Davies, K. J. A. (2017) · Physiological Reviews · doi:10.1152/physrev.00033.2016 · Cited by 149
Wang, F., Xia, X., Yang, C., Shen, J., Mai, J., Kim, H.-C., Kirui, D., Kang, Y., Fleming, J. B., Koay, E. J., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3435 · Cited by 160
“SMAD4 depletion causes persistent ROS increase in pancreatic cancer cells after irradiation exposure It has been previously reported that autophagy occurs in response to stress, such as ROS (37, 38) and nutrient starvation (39).”
BackgroundChen, Y., Luo, G., Jiao, Y., Wang, Y., Yang, X., Wang, X., Li, G., Liu, Z., & Zhong, N. (2014) · Mediators of Inflammation · doi:10.1155/2014/426740 · Cited by 151
“Autophagy pathway is activated under environmental stress conditions [40].”
BackgroundMitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator
Chong, S. J. F., Low, I. C. C., & Pervaiz, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.06.002 · Cited by 142
“…mitoROS have been shown to participate in cellular activities such as hypoxia adaptation (Chandel et al., 1998, 2000), autophagy (Qi et al., 2012; Scherz-Shouval et al., 2007), immunity (Arsenijevic et al., 2000; Emre et al., 2007; Mailloux and Harper, 2011) as well as cell differentiation…”
InfluentialThe cell biology of autophagy in metazoans: a developing story
Meléndez, A., & Neufeld, T. P. (2008) · Development · doi:10.1242/dev.016105 · Cited by 145
“By contrast, flies with mutations in Drosophila Atg7 or Atg8a develop to adulthood, and mice with mutations in Atg4C, Atg5, Atg7 or Bif-1 progress through embryonic development in normal numbers, although in each of these cases, serious defects are observed postnatally (see below) (Juhász et al., 2007; Komatsu et al.,…”
InfluentialHigh Mobility Group Box 1 (HMGB1) Activates an Autophagic Response to Oxidative Stress
Tang, D., Kang, R., Livesey, K. M., Zeh, H. J., & Lotze, M. T. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3666 · Cited by 146
“ROS can induce autophagy (1) through several distinct mechanisms involving autophagy-related gene 4 (ATG4) (36), catalase (50), and the mitochondrial electron transport chain (7).”
Tisi, A., Feligioni, M., Passacantando, M., Ciancaglini, M., & Maccarone, R. (2021) · Cells · doi:10.3390/cells10010064 · Cited by 144
“Moreover, it has been demonstrated that oxidative stress is a major inductor of autophagy [52].”
BackgroundReactive Molecule Species and Antioxidative Mechanisms in Normal Skin and Skin Aging
Wölfle, U., Seelinger, G., Bauer, G., Meinke, M. C., Lademann, J., & Schempp, C. M. (2014) · Skin Pharmacology and Physiology · doi:10.1159/000360092 · Cited by 142
Dagda, R. K., Gusdon, A. M., Pien, I., Strack, S., Green, S., Li, C., Houten, B. V., Cherra, S. J., & Chu, C. T. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.74 · Cited by 146
“Given the caveats associated with fluorescent ROS indicators, we confirmed these results by transfection with a mitochondrially-targeted bacterial hydrogen peroxide sensing regulatory domain (mito-HyPer) (Supplementary Figure 4).”
InfluentialUpregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity
Dutta, D., Xu, J., Js, K., Dunn, W. A., & Leeuwenburgh, C. (2013) · Autophagy · doi:10.4161/auto.22971 · Cited by 143
“Importantly, some findings suggest that mitochondrial stress and ROS per se can act as inducers of autophagy.(19,34,62) Such autophagic induction could be thought of chronic administration of antioxidants such as vitamin A, vitamin E or β-carotene.”
BackgroundOxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis
Sharma, P., Kaushal, N., Saleth, L. R., Ghavami, S., Dhingra, S., & Kaur, P. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166742 · Cited by 148
Reactive Oxygen Species, Cancer and Anti-Cancer Therapies
Nechifor, M. T., Neagu, T.-M., & Manda, G. (2009) · Current Chemical Biology · doi:10.2174/2212796810903010022 · Cited by 142
Timosaponin A-III Induces Autophagy Preceding Mitochondria-Mediated Apoptosis in HeLa Cancer Cells
Sy, L., Yan, S., Lok, C., Man, R. Y. K., & Che, C. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1983 · Cited by 142
“In this study, TAIII treatment markedly induced ROS production, which has been suggested to be essential for both autophagy and apoptosis ( 26 , 27).”
BackgroundInfluentialRedox-Mediated Mechanism of Chemoresistance in Cancer Cells
Kim, E.-K., Jang, M., Song, M.-J., Kim, D., Kim, Y., & Jang, H. H. (2019) · Antioxidants · doi:10.3390/antiox8100471 · Cited by 141
Oxidative stress in cardiac hypertrophy: From molecular mechanisms to novel therapeutic targets
Ramachandra, C. J. A., Cong, S., Chan, X., Yap, E. P., Fan, Y., & Hausenloy, D. J. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.040 · Cited by 140
Kotsias, F., Hoffmann, E., Amigorena, S., & Savina, A. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4557 · Cited by 142
“In a starvation-induced autophagy model, superoxide and H 2 O 2 lead to autophagy by inhibiting the Atg4 cysteine protease oxidizing reversibly the cysteine residue within the enzymatic active site (116).”
Chien, C.-T., Shyue, S.-K., & Lai, M.-K. (2007) · Transplantation · doi:10.1097/01.tp.0000287334.38933.e3 · Cited by 138
“contributing to abnormal signal transduction or cellular dysfunction (5, 6) and trigger the cascade of apoptosis, autophagy, and necrosis (2, 7, 8).”
BackgroundThe interplay between autophagy and apoptosis in the diabetic heart
Ouyang, C., You, J., & Xie, Z. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.10.014 · Cited by 136
Autophagy and cardiac diseases: Therapeutic potential of natural products
Wu, X., Liu, Z., Yu, X., Xu, S., & Luo, J. (2020) · Medicinal Research Reviews · doi:10.1002/med.21733 · Cited by 137
“As an example, redox regulation of Atg4 at cysteine 81 inhibits its protease activity, thereby promoting LC3 lipidation and autophagosome formation.(55) It should be noted that ROS is a double‐edged sword on the regulation of autophagy, as the physiological level of ROS is required for autophagy activation in both car…”
BackgroundA mammosphere formation RNAi screen reveals that ATG4A promotes a breast cancer stem-like phenotype
Wolf, J. M., Dewi, D. L., Fredebohm, J., Müller‐Decker, K., Flechtenmacher, C., Hoheisel, J. D., & Boettcher, M. (2013) · Breast Cancer Research · doi:10.1186/bcr3576 · Cited by 137
“ATG4A can cleave ATG8 near its C-terminus allowing the conjugation of ATG8 to phosphatidylethanolamine and subsequently to the membrane of the autophagosome [44].”
BackgroundHigh Glucose Induces Bone Marrow-Derived Mesenchymal Stem Cell Senescence by Upregulating Autophagy
Chang, T.-C., Hsu, M., & Wu, K. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126537 · Cited by 141
Yu, W., Wang, Y., Zhu, J., Jin, L., Liu, B., Xia, K., Wang, J., Gao, J., Liang, C., & Tao, H. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.11.019 · Cited by 140
Regulation of A20 and other OTU deubiquitinases by reversible oxidation
Kulathu, Y., García, F., Mevissen, T. E. T., Busch, M., Arnaudo, N., Carroll, K. S., Barford, D., & Komander, D. (2013) · Nature Communications · doi:10.1038/ncomms2567 · Cited by 141
The Relationship of Redox With Hallmarks of Cancer: The Importance of Homeostasis and Context
Xing, F., Hu, Q., Qin, Y., Xu, J., Zhang, B., Yu, X., & Wang, W. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.862743 · Cited by 142
“H2O2 can promote the accumulation of LC3-PE by inhibiting the delipidating activity of ATG4 in the cytoplasm and induce autophagy in cells during amino acid starvation (104).”
BackgroundAutophagy pathways activated in response to PDT contribute to cell resistance against ROS damage
Dewaele, M., Martinet, W., Rubio, N., Verfaillie, T., de Witte, P. A. M., Piette, J. G., & Agostinis, P. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01118.x · Cited by 139
“Different ROS generating molecules or signals known to promote apoptosis have recently been shown to instigate MA [2, 8–14] as well as CMA [15, 16].”
BackgroundAutophagy and Cancer Metabolism
Goldsmith, J., Levine, B., & Debnath, J. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-416618-9.00002-9 · Cited by 139
“Most directly, ROS inhibit ATG4 autophagosome turnover activity, allowing for the maintenance of lipidated LC3 necessary for autophagosome formation (Scherz-Shouval et al., 2007).”
BackgroundAutophagy in lung disease pathogenesis and therapeutics
Ryter, S. W., & Choi, A. M. K. (2015) · Redox Biology · doi:10.1016/j.redox.2014.12.010 · Cited by 140
“, ATG4B) may be subjected to direct redox regulation [64].”
BackgroundCadmium-Based Quantum Dot Induced Autophagy Formation for Cell Survival via Oxidative Stress
Luo, Y.-H., Wu, S., Wei, Y., Chen, Y.-C., Tsai, M., Ho, C.-C., Lin, S., Yang, C., & Lin, P. (2013) · Chemical Research in Toxicology · doi:10.1021/tx300455k · Cited by 135
HIV-1 gp41 fusogenic function triggers autophagy in uninfected cells
Denizot, M., Varbanov, M., Espert, L., Robert-Hebmann, V., Sagnier, S., García, E., Curriu, M., Mamoun, R. Z., Blanco, J., & Biard‐Piechaczyk, M. (2008) · Autophagy · doi:10.4161/auto.6880 · Cited by 134
ERp57/GRP58: A protein with multiple functions
Turano, C., Gaucci, E., Grillo, C., & Chichiarelli, S. (2011) · Cellular & Molecular Biology Letters · doi:10.2478/s11658-011-0022-z · Cited by 135
“Starvation has been shown to induce oxidative stress [66].”
BackgroundPark, S., Kim, J.-H., Chi, G. Y., Kim, G., Chang, Y., Moon, S., Nam, S., Kim, W., Yoo, Y. H., & Choi, Y. H. (2012) · Toxicology Letters · doi:10.1016/j.toxlet.2012.06.007 · Cited by 134
“All rights reserved. types of cancer cells (Scherz-Shouval et al., 2007; Gao et al., 2008).”
BackgroundLionaki, E., Markaki, M., Palikaras, K., & Tavernarakis, N. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.04.010 · Cited by 137
“thus increasing autophagosome formation [83].”
BackgroundTargeting ROS-Mediated Crosstalk Between Autophagy and Apoptosis in Cancer
Gao, L., Loveless, J., Shay, C., & Teng, Y. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-42667-5_1 · Cited by 135
Trejo‐Solís, C., Jiménez‐Farfán, D., Rodríguez‐Enríquez, S., Fernández‐Valverde, F., Cruz-Salgado, A., Ruíz-Azuara, L., & Sotelo, J. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-156 · Cited by 133
“Interestingly, it has been shown that the activation of JNK results in the phosphorylation of Bcl-2 which enhances autophagy and cell survival by disrupting the interaction between Bcl-2 and Beclin1, while prolonged Bcl-2 phosphorylation mediated by JNK promotes apoptosis [51].”
BackgroundInfluential
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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