Abstract
Reactive oxygen species (ROS) used to be perceived as harmful cellular weaponry designed to eliminate pathogens, whereas autophagy as the process for the disintegration and re-utilization of cytoplasm. Both pathways respond to cellular stress and are evolutionary conserved, ubiquitous in modern organisms, necessary for development and important in the pathogeny of chronic diseases. The activity of the ROS pathway depends on spatial confinement of its proteins, the exposition of sensor’s cysteines to the solvent of regulatory proteins, the oxidation-driven conformational and oligomeric change of these proteins, and the limitation of the diffusion of ROS. ROS determine autophagy pathway activity exerting similar changes on crucial autophagy proteins, namely, ATG4, 3, 7, and 8, as well as the regulatory proteins AMPK and mTOR. The intricated relationship of ROS and autophagy pathways is determinant for the proper functioning of both pathways.
This is a preview of subscription content, log in via an institution to check access.
References
Avivar-Valderas A, Salas E, Bobrovnikova-Marjon E, Diehl JA, Nagi C, Debnath J et al (2011) PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment. Mol Cell Biol 31:3616–3629. https://doi.org/10.1128/mcb.05164-11
Baba M, Takeshige K, Baba N, Ohsumi Y (1994) Ultrastructural analysis of the autophagic process in yeast: detection of autophagosomes and their characterization. J Cell Biol 124:903–913. https://doi.org/10.1083/jcb.124.6.903
Baird L, Yamamoto M (2020) The molecular mechanisms regulating the KEAP1-NRF2 pathway. Mol Cell Biol 40:In press. https://doi.org/10.1128/mcb.00099-20
Bartosz G (2009) Reactive oxygen species: destroyers or messengers? Biochem Pharmacol 77:1303–1315. https://doi.org/10.1016/j.bcp.2008.11.009
Behring JB, van der Post S, Mooradian AD, Egan MJ, Zimmerman MI, Clements JL et al (2020) Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation. Sci Signal 13:eaay7315. https://doi.org/10.1126/scisignal.aay7315
Bisht S, Faiq M, Tolahunase M, Dada R (2017) Oxidative stress and male infertility. Nat Rev Urol 14:470–485. https://doi.org/10.1038/nrurol.2017.69
Cao Y, Wang J, Tian H, Fu G-H (2020) Mitochondrial ROS accumulation inhibiting JAK2/STAT3 pathway is a critical modulator of CYT997-induced autophagy and apoptosis in gastric cancer. J Exp Clin Cancer Res 39:119. https://doi.org/10.1186/s13046-020-01621-y
Cruz-Garcia D, Brouwers N, Malhotra V, Curwin AJ (2020) Reactive oxygen species triggers unconventional secretion of antioxidants and Acb1. J Cell Biol 219:e201905028. https://doi.org/10.1083/jcb.201905028
D’Autréaux B, Toledano MB (2007) ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8:813–824. https://doi.org/10.1038/nrm2256
de Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492. https://doi.org/10.1146/annurev.ph.28.030166.002251
Dooley HC, Razi M, Polson HEJ, Girardin SE, Wilson MI, Tooze SA (2014) WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol Cell 55:238–252. https://doi.org/10.1016/j.molcel.2014.05.021
Edgar RS, Green EW, Zhao Y, van Ooijen G, Olmedo M, Qin X et al (2012) Peroxiredoxins are conserved markers of circadian rhythms. Nature 485:459–464. https://doi.org/10.1038/nature11088
Errafiy R, Aguado C, Ghislat G, Esteve JM, Gil A, Loutfi M et al (2013) PTEN increases autophagy and inhibits the ubiquitin-proteasome pathway in glioma cells independently of its lipid phosphatase activity. PLoS One 8:e83318. https://doi.org/10.1371/journal.pone.0083318
Finkel T (2011) Signal transduction by reactive oxygen species. J Cell Biol 194:7–15. https://doi.org/10.1083/jcb.201102095
Funato Y, Terabayashi T, Sakamoto R, Okuzaki D, Ichise H, Nojima H et al (2010) Nucleoredoxin sustains Wnt/β-catenin signaling by retaining a pool of inactive dishevelled protein. Curr Biol 20:1945–1952. https://doi.org/10.1016/j.cub.2010.09.065
Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AHV, Taanman JW (2010) Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet 19:4861–4870. https://doi.org/10.1093/hmg/ddq419
Han D, Ybanez MD, Ahmadi S, Yeh K, Kaplowitz N (2009) Redox regulation of tumor necrosis factor signaling. Antioxid Redox Signal 11:2245–2263. https://doi.org/10.1089/ars.2009.2611
He C, Levine B (2010) The Beclin 1 interactome. Curr Opin Cell Biol 22:140–149. https://doi.org/10.1016/j.ceb.2010.01.001
Hinchy EC, Gruszczyk AV, Willows R, Navaratnam N, Hall AR, Bates G et al (2018) Mitochondria-derived ROS activate AMP-activated protein kinase (AMPK) indirectly. J Biol Chem 293:17208–17217. https://doi.org/10.1074/jbc.RA118.002579
Homma T, Fujii J (2015) Application of glutathione as anti-oxidative and anti-aging drugs. Curr Drug Metab 16:560–571. https://doi.org/10.2174/1389200216666151015114515
Hong L, Sun Y, An JZ, Wang C, Qiao SG (2020) Sevoflurane preconditioning confers delayed cardioprotection by upregulating AMP-activated protein kinase levels to restore autophagic flux in ischemia-reperfusion rat hearts. Med Sci Monit 26:e922176. https://doi.org/10.12659/MSM.922176
Jain A, Lamark T, Sjøttem E, Larsen KB, Awuh JA, Øvervatn A et al (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285:22576–22591. https://doi.org/10.1074/jbc.M110.118976
Jung CH, Jun CB, Ro S-H, Kim Y-M, Otto NM, Cao J et al (2009) ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20:1992–2003. https://doi.org/10.1091/mbc.e08-12-1249
Kim J, Kundu M, Viollet B, Guan K-L (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13:132–141. https://doi.org/10.1038/ncb2152
Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8:931–937. https://doi.org/10.1038/nrm2245
Kuma A, Mizushima N, Ishihara N, Ohsumi Y (2002) Formation of the ∼350-kDa Apg12-Apg5·Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. J Biol Chem 277:18619–18625. https://doi.org/10.1074/jbc.M111889200
Li W, Li J, Bao J (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69:1125–1136. https://doi.org/10.1007/s00018-011-0865-5
Li J, Jiang M, Zhou H, Jin P, Cheung KMC, Chu PK et al (2019) Vanadium dioxide nanocoating induces tumor cell death through mitochondrial electron transport chain interruption. Glob Chall 1800058:1–14. https://doi.org/10.1002/gch2.201800058
Massey A, Kiffin R, Cuervo AM (2004) Pathophysiology of chaperone-mediated autophagy. Int J Biochem Cell Biol 36:2420–2434. https://doi.org/10.1016/j.biocel.2004.04.010
Matsuzaki H, Ichino A, Hayashi T, Yamamoto T, Kikkawa U (2005) Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family. J Biochem 138:485–491. https://doi.org/10.1093/jb/mvi146
Mizushima N (2007) Autophagy: process and function. Genes Dev 21:2861–2873. https://doi.org/10.1101/gad.1599207
Nakamura S, Yoshimori T (2017) New insights into autophagosome–lysosome fusion. J Cell Sci 130:1209–1216. https://doi.org/10.1242/jcs.196352
Nakatogawa H (2020) Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol 21:439–458. https://doi.org/10.1038/s41580-020-0241-0
Nguyen GT, Shaban L, Mack M, Swanson KD, Bunnell SC, Sykes DB et al (2020) Skap2 is required for defense against k. Pneumoniae infection and neutrophil respiratory burst. elife 9:1–28. https://doi.org/10.7554/eLife.56656
Nishimura T, Tamura N, Kono N, Shimanaka Y, Arai H, Yamamoto H et al (2017) Autophagosome formation is initiated at phosphatidylinositol synthase-enriched <scp>ER</scp> subdomains. EMBO J 36:1719–1735. https://doi.org/10.15252/embj.201695189
Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H et al (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy*[S]. J Biol Chem 282:24131–24145. https://doi.org/10.1074/jbc.M702824200
Planavsky NJ, Robbins LJ, Kamber BS, Schoenberg R (2020) Weathering, alteration and reconstructing Earth’s oxygenation. Interface Focus 10:20190140. https://doi.org/10.1098/rsfs.2019.0140
Puissant A, Fenouille N, Auberger P (2012) When autophagy meets cancer through p62/SQSTM1. Am J Cancer Res 2:397–413
Rawet Slobodkin M, Elazar Z (2013) The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy. Essays Biochem 55:51–64. https://doi.org/10.1042/BSE0550051
Scherz-Shouval R, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 17:422–427. https://doi.org/10.1016/j.tcb.2007.07.009
Scherz-Shouval R, Elazar Z (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36:30–38. https://doi.org/10.1016/j.tibs.2010.07.007
Scherz-Shouval R, Shvets E, Elazar Z (2007a) Oxidation as a post-translational modification that regulates autophagy. Autophagy 3:371–373. https://doi.org/10.4161/auto.4214
Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007b) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26:1749–1760. https://doi.org/10.1038/sj.emboj.7601623
Sedlackova L, Korolchuk VI (2020) The crosstalk of NAD, ROS and autophagy in cellular health and ageing. Biogerontology 21:381–397. https://doi.org/10.1007/s10522-020-09864-0
Semenza GL (2011) Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning. Biochim Biophys Acta, Mol Cell Res 1813:1263–1268. https://doi.org/10.1016/J.BBAMCR.2010.08.006
Sheng R, Qin ZH (2019) History and current status of autophagy research. Adv Exp Med Biol 1206, Springer, Singapore:3–37. https://doi.org/10.1007/978-981-15-0602-4_1
Shiau D-J, Kuo W-T, Davuluri GVN, Shieh C-C, Tsai P-J, Chen C-C et al (2020) Hepatocellular carcinoma-derived high mobility group box 1 triggers M2 macrophage polarization via a TLR2/NOX2/autophagy axis. Sci Rep 10:13582. https://doi.org/10.1038/s41598-020-70137-4
Sinha RA, Singh BK, Zhou J, Wu Y, Farah BL, Ohba K et al (2015) Thyroid hormone induction of mitochondrial activity is coupled to mitophagy via ROS-AMPKULK1 signaling. Autophagy 11:1341–1357. https://doi.org/10.1080/15548627.2015.1061849
Sohal RS, Allen RG (1990) Oxidative stress as a causal factor in differentiation and aging: a unifying hypothesis. Exp Gerontol 25:499–522. https://doi.org/10.1016/0531-5565(90)90017-V
Storz P (2003) Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway. EMBO J 22:109–120. https://doi.org/10.1093/emboj/cdg009
Tönnies E, Trushina E (2017) Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 57:1105–1121. https://doi.org/10.3233/JAD-161088
Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174. https://doi.org/10.1016/0014-5793(93)80398-E
Xu X, Zhi T, Chao H, Jiang K, Liu Y, Bao Z et al (2018) ERK1/2/mTOR/Stat3 pathway-mediated autophagy alleviates traumatic brain injury-induced acute lung injury. Biochim Biophys Acta Mol basis Dis 1864:1663–1674. https://doi.org/10.1016/j.bbadis.2018.02.011
Zhou YY, Li Y, Jiang WQ, Zhou LF (2015) MAPK/JNK signalling: a potential autophagy regulation pathway. Biosci Rep 35:1–10. https://doi.org/10.1042/BSR20140141
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Singapore Pte Ltd.
About this entry
Cite this entry
Campos-Blázquez, J. et al. (2021). Relationship Between ROS, Autophagy, and Cancer. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_167-1
Download citation
DOI: https://doi.org/10.1007/978-981-15-4501-6_167-1
Received:
Accepted:
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-4501-6
Online ISBN: 978-981-15-4501-6
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences