P62: intersection of antioxidant defense and autophagy pathways

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Numerous regulatory cascades link the cell´s response to oxidative stress and the mechanisms of maintaining homeostasis and cell viability. The review summarizes the molecular mechanisms of interaction of the autophagy protein p62 with cell defense systems, primarily through the NRF2/KEAP1/ARE pathway. Understanding the cross-regulation of antioxidant defense and autophagy pathways contributes to the search for promising molecular targets for the treatment of age-related diseases.

Full Text

Restricted Access

About the authors

G. A. Shilovsky

Lomonosov Moscow State University; Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences

Author for correspondence.
Email: gregory_sh@list.ru

Faculty of Biology

Russian Federation, Moscow, 119234; Moscow, 127051

References

  1. Zhang W., Feng C., Jiang H. (2021) Novel target for treating Alzheimer´s diseases: crosstalk between the Nrf2 pathway and autophagy. Ageing Res. Rev. 65, 101207. doi: 10.1016/j.arr.2020.101207
  2. Shakya A., McKee N.W., Dodson M., Chapman E., Zhang D.D. (2023) Anti-ferroptotic effects of Nrf2: beyond the antioxidant response. Mol. Cells. 46, 165–175. doi: 10.14348/molcells.2023.0005
  3. Baykal-Köse S., Efe H., Yüce Z. (2021) Аутофагия не влияет на ответ линии клеток хронического миелоидного лейкоза, устойчивой к иматинибу, на ингибиторы тирозинкиназ. Молекуляр. биология. 55(4), 626–633. doi: 10.31857/S002689842104004
  4. Зиновкин Р.А., Гребенчиков О.А. (2020) Активация транскрипционного фактора Nrf2 как подход к предотвращению цитокинового шторма при COVID-19. Биохимия. 85(7), 978–983. doi: 10.31857/S0320972520070118
  5. Шиловский Г.А., Путятина Т.С, Моргунова Г.В., Селиверстов А.В., Ашапкин В.В., Сорокина Е.В., Марков А.В., Скулачев В.П. (2021) Регуляция белков циркадных ритмов и nrf2-опосредованной антиоксидантной защиты: двойная роль киназы гликогенсинтазы 3. Биохимия. 86(4), 511–528. doi: 10.31857/S0320972521040059
  6. Зиновкин Р.А., Кондратенко Н.Д., Зиновкина Л.А. (2022) Является ли Nrf2 основным регулятором старения млекопитающих? Биохимия. 87(12), 1842–1855. doi: 10.31857/S0320972522120053
  7. Шиловский Г.А. (2022) Лабильность защитной системы клетки Nrf2/Keap/ARE в различных моделях клеточного старения возрастных патологиях. Биохимия. 87(1), 86–103. doi: 10.31857/S0320972522010067
  8. Кондратенко Н.Д., Зиновкина Л.А., Зиновкин Р.А. (2023) Транскрипционный фактор NRF2 в функционировании эндотелия. Молекуляр. биология. 57(6), 1058–1076. doi: 10.31857/S0026898423060101
  9. Cloer E.W., Siesser P.F., Cousins E.M., Goldfarb D., Mowrey D.D., Harrison J.S., Weir S.J., Dokholyan N.V., Major M.B. (2018) p62-dependent phase separation of patient-derived Keap1 mutations Nrf2. Mol. Cell. Biol. 38(22), e00644-17. doi: 10.1128/MCB.00644-17
  10. Lo S.-C., Hannink M. (2006) PGAM5, a Bcl-XL-interacting protein, is a novel substrate for the redox-regulated Keap1-dependent ubiquitin ligase complex. J. Biol. Chem. 281, 37893–37903. doi: 10.1074/jbc.M606539200
  11. O´Mealey G.B., Plafker K.S., Berry W.L., Janknecht R., Chan J.Y., Plafker S.M. (2017) A PGAM5-Keap1-Nrf2 complex is required for stress-induced mitochondrial retrograde trafficking. J. Cell Sci. 130, 3467–3480. doi: 10.1242/jcs.203216
  12. Yamada T., Murata D., Adachi Y., Itoh K., Kameoka S., Igarashi A., Kato T., Araki Y., Huganir R.L., Dawson T.M., Yanagawa T., Okamoto K., Iijima M., Sesaki H. (2018) Mitochondrial stasis reveals p62-mediated ubiquitination in PARKIN-independent mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab. 28, 588–604.e5. doi: 10.1016/j.cmet.2018.06.014
  13. Rada P., Rojo A.I., Evrard-Todeschi N., Innamorato N.G., Cotte A., Jaworski T., Tobón-Velasco J.C., Devijver H., García-Mayoral M.F., Van Leuven F., Hayes J.D., Bertho G., Cuadrado A. (2012) Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/β-TrCP axis. Mol. Cell. Biol. 32(17), 3486–3499. doi: 10.1128/MCB.00180-12
  14. Komatsu M., Kurokawa H., Waguri S., Taguchi K., Kobayashi A., Ichimura Y., Sou Y.S., Ueno I., Sakamoto A., Tong K.I., Kim M., Nishito Y., Iemura S., Natsume T., Ueno T., Kominami E., Motohashi H., Tanaka K., Yamamoto M. (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 12(3), 213–223. doi: 10.1038/ncb2021
  15. Jain A., Lamark T., Sjøttem E., Larsen K.B., Awuh JA., Øvervatn A., McMahon M., Hayes J.D., Johansen T. (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(29), 22576–22591. doi: 10.1074/jbc.M110.118976
  16. Lamark T., Svenning S., Johansen T. (2017) Regulation of selective autophagy: the p62/SQSTM1 paradigm. Essays Biochem. 61, 609–624. doi: 10.1042/EBC20170035
  17. Taguchi K., Fujikawa N., Komatsu M., Ishii T., Unno M., Akaike T., Motohashi H., Yamamoto M. (2012) Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc. Natl. Acad. Sci. USA. 109, 13561–13566. doi: 10.1073/pnas.1121572109
  18. Zhang D.D., Lo S.-C., Sun Z., Habib G.M., Lieberman M.W., Hannink M. (2005) Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. J. Biol. Chem. 280, 30091–30099. doi: 10.1074/jbc.M501279200
  19. Duran A., Amanchy R., Linares J.F., Joshi J., Abu-Baker S., Porollo A., Hansen M., Moscat J., Diaz-Meco M.T. (2011) p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol. Cell. 44(1), 134–146. doi: 10.1016/j.molcel.2011.06.038
  20. Switon K., Kotulska K., Janusz-Kaminska A., Zmorzynska J., Jaworski J. (2017) Molecular neurobiology of mTOR. Neuroscience. 341, 112–153. doi: 10.1016/j.neuroscience.2016.11.017
  21. Murugan A.K. (2019) mTOR: Role in cancer, metastasis and drug resistance. Semin. Cancer Biol. 59, 92–111. doi: 10.1016/j.semcancer.2019.07.003
  22. Kim J., Cha Y.-N., Surh Y.-J. (2010) A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat. Res. 690(1–2), 12–23. doi: 10.1016/j.mrfmmm.2009.09.007
  23. Pickering A.M., Linder R.A., Zhang H., Forman H.J., Davies K.J.A. (2012) Nrf2-dependent induction of proteasome and Pa28αβ regulator ARE required for adaptation to oxidative stress. J. Biol. Chem. 287(13), 10021–10031. doi: 10.1074/jbc.M111.277145
  24. Ghanim B.Y., Qinna N.A. (2022) Nrf2/ARE axis signalling in hepatocyte cellular death. Mol. Biol. Rep. 49(5), 4039–4053. doi: 10.1007/s11033-022-07125-6
  25. Johansen T., Lamark T. (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy. 7, 279–296. doi: 10.4161/auto.7.3.14487
  26. Copple I.M., Lister A., Obeng A.D., Kitteringham N.R., Jenkins R.E., Layfield R., Foster B.J., Goldring C.E., Park B.K. (2010) Physical functional interaction of sequestosome 1 with Keap1 regulates the Keap1–Nrf2 cell defense pathway. J. Biol. Chem. 285, 16782–16788. doi: 10.1074/jbc.M109.096545
  27. Katsuragi Y., Ichimura Y., Komatsu M. (2015) p62/SQSTM1 functions as a signaling hub and an autophagy adaptor. FEBS J. 282, 4672–4678.
  28. Carroll B., Otten E.G., Manni D., Stefanatos R., Menzies F.M., Smith G.R., Jurk D., Kenneth N., Wilkinson S., Passos J.F., Attems J., Veal E.A., Teyssou E., Seilhean D., Millecamps S., Eskelinen E.L., Bronowska A.K., Rubinsztein D.C., Sanz A., Korolchuk V.I. (2018) Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis. Nat. Commun. 9, 256. doi: 10.1038/s41467-017-02746-z
  29. Rogov V., Dotsch V., Johansen T., Kirkin V. (2014) Interactions between autophagy receptors and ubiquitin like proteins form the molecular basis for selective autophagy. Mol. Cell. 53(2), 167–178. doi: 10.1016/j.molcel.2013.12.014
  30. Dokladny K., Zuhl M.N., Mandell M., Bhattacharya D., Schneider S., Deretic V., Moseley P.L. (2013) Regulatory coordination between two major intracellular homeostatic systems: heat shock response autophagy. J. Biol. Chem. 288(21), 14959–14972. doi: 10.1074/jbc.M113.462408
  31. Krämer L., Groh C., Herrmann J.M. (2021) The proteasome: friend and foe of mitochondrial biogenesis. FEBS Lett. 595(8), 1223–1238. doi: 10.1002/1873-3468.14010
  32. Jin S.M., Lazarou M., Wang C., Kane L.A., Narendra D.P., Youle R.J. (2010) Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL. J. Cell Biol. 191, 933–942. doi: 10.1083/jcb.201008084
  33. Novak I. (2012) Mitophagy: a complex mechanism of mitochondrial removal. Antioxid. Redox Signal. 17(5), 794–802. doi: 10.1089/ars.2011.4407
  34. Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. (1999) The interaction of p62 with RIP links the atypical PKCs to NF-κB activation. EMBO J. 18(11), 3044–3053. doi: 10.1093/emboj/18.11.3044
  35. Choe J.Y., Jung H.Y., Park K.Y., Kim S.K. (2014) Enhanced p62 expression through impaired proteasomal degradation is involved in caspase-1 activation in monosodium urate crystal-induced interleukin-1β expression. Rheumatology (Oxford). 53(6), 1043–1053. doi: 10.1093/rheumatology/ket474
  36. Geisler S., Holmström K.M., Skujat D., Fiesel F.C., Rothfuss O.C., Kahle P.J., Springer W. (2010) PINK1/PARKIN-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 12, 119–131. doi: 10.1038/ncb2012
  37. Yamada T., Dawson T.M., Yanagawa T., Iijima M., Sesaki H. (2019) SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/PARKIN in mitophagy. Autophagy. 15, 2012–2018. doi: 10.1080/15548627.2019.1643185
  38. Sulkshane P., Ram J., Thakur A., Reis N., Kleifeld O., Glickman M.H. (2021) Ubiquitination and receptor-mediated mitophagy converge to eliminate oxidation-damaged mitochondria during hypoxia. Redox Biol. 45, 102047. doi: 10.1016/j.redox.2021.102047
  39. Chu C.T. (2019) Mechanisms of selective autophagy and mitophagy: implications for neurodegenerative diseases. Neurobiol. Dis. 122, 23–34. doi: 10.1016/j.nbd.2018.07.015
  40. Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H., Øvervatn A., Bjørkøy G., Johansen T. (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J. Biol. Chem. 282(33), 24131–24145. doi: 10.1074/jbc.M702824200
  41. Boyle K.B., Randow F. (2013) The role of “eat-me” signals and autophagy cargo receptors in innate immunity. Curr. Opin. Microbiol. 16(3), 339–348. doi: 10.1016/j.mib.2013.03.010
  42. Korac J., Schaeffer V., Kovacevic I., Clement A.M., Jungblut B., Behl C., Terzic J., Dikic I. (2013) Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates. J. Cell Sci. 126(Pt. 2), 580–592. doi: 10.1242/jcs.114926
  43. Jo C., Gundemir S., Pritchard S., Jin Y.N., Rahman I., Johnson G.V. (2014) Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. Nat. Commun. 5, 3496. doi: 10.1038/ncomms4496
  44. Inomata M., Niida S., Shibata K., Into T. (2012) Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20. Cell. Mol. Life Sci. 69(6), 963–979. doi: 10.1007/s00018-011-0819-y
  45. Yang M., Wang L., Chen C., Guo X., Lin C., Huang W., Chen L. (2021) Genome-wide analysis of autophagy-related genes in Medicago truncatula highlights their roles in seed development and response to drought stress. Sci. Rep. 11(1), 22933. doi: 10.1038/s41598-021-02239-6
  46. Zhou J., Wang J., Cheng Y., Chi Y.J., Fan B., Yu J.Q., Chen Z. (2013) NBR1-mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses. PLoS Genet. 9(1), e1003196. doi: 10.1371/journal.pgen.1003196
  47. Zientara-Rytter K., Sirko A. (2014) Significant role of PB1 and UBA domains in multimerization of Joka2, a selective autophagy cargo receptor from tobacco. Front. Plant Sci. 5, 13. doi: 10.3389/fpls.2014.00013
  48. Long J., Garner T.P., Pandya M.J., Craven C.J., Chen P., Shaw B., Williamson M.P., Layfield R., Searle M.S. (2010) Dimerisation of the UBA domain of p62 inhibits ubiquitinbinding and regulates NF-B signalling. J. Mol. Biol. 396(1), 178–194. doi: 10.1016/j.jmb.2009.11.032
  49. Matsumoto G., Shimogori T., Hattori N., Nukina N. (2015) TBK1 controls autophagosomal engulfment of polyubiquitinated mitochondria through p62/SQSTM1 phosphorylation. Hum. Mol. Genet. 24(15), 4429–4442. doi: 10.1093/hmg/ddv179
  50. Wurzer B., Zaffagnini G., Fracchiolla D., Turco E., Abert C., Romanov J., Martens S. (2015) Oligomerization of p62 allows for selection of ubiquitinated cargo and isolation membrane during selective autophagy. Elife. 4, e08941. doi: 10.7554/eLife.08941
  51. Nagy P., Hegedus K., Pircs K., Varga A., Juhasz G. (2014) Different effects of Atg2 and Atg18 mutations on Atg8a and Atg9 trafficking during starvation in Drosophila. FEBS Lett. 588(3), 408–413. doi: 10.1016/j.febslet.2013.12.012
  52. Nagy P., Kárpáti M., Varga A., Pircs K., Venkei Z., Takáts S., Varga K., Erdi B., Hegedűs K, Juhász G. (2014) Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila. Autophagy. 10(3), 453–467. doi: 10.4161/auto.27442
  53. Hennig P., Fenini G., Di Filippo M., Karakaya T., Beer H.D. (2021) The pathways underlying the multiple roles of p62 in inflammation and cancer. Biomedicines. 9(7), 707. doi: 10.3390/biomedicines9070707
  54. Panwar V., Singh A., Bhatt M., Tonk R.K., Azizov S., Raza A.S., Sengupta S., Kumar D., Garg M. (2023) Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease. Signal Transduct. Target. Ther. 8(1), 375. doi: 10.1038/s41392-023-01608-z
  55. Juhász G. (2012) Interpretation of bafilomycin, pH neutralizing or protease inhibitor treatments in autophagic flux experiments: novel considerations. Autophagy. 8(12), 1875–1876. doi: 10.4161/auto.21544
  56. Danieli A., Martens S. (2018) p62-mediated phase separation at the intersection of the ubiquitin-proteasome system autophagy. J. Cell Sci. 131(19), jcs214304. doi: 10.1242/jcs.214304
  57. Pai Y.L., Lin Y.J., Peng W.H., Huang L.T., Chou H.Y., Wang C.H., Chien C.T., Chen G.C. (2023) The deubiquitinase Leon/USP5 interacts with Atg1/ULK1 and antagonizes autophagy. Cell Death Dis. 14(8), 540. doi: 10.1038/s41419-023-06062-x
  58. Yan J., Seibenhener M.L. Calderilla-Barbosa L., Diaz-Meco M.T., Moscat J., Jiang J., Wooten M.W., Wooten M.C. (2013) SQSTM1/p62 interacts with HDAC6 and regulates deacetylase activity. PLoS One. 278(9), e76016. doi: 10.1371/journal.pone.0076016
  59. Nihira K., Miki Y., Ono K., Suzuki T., Sasano H. (2014) An inhibition of p62/SQSTM1 caused autophagic cell death of several human carcinoma cells. Cancer Sci. 105(5), 568–575. doi: 10.1111/cas.12396
  60. Pankiv S., Lamark T., Bruun J.A., Øvervatn A., Bjørkøy G., Johansen T. (2010) Nucleocytoplasmic shuttling of p62/SQSTM1 and its role in recruitment of nuclear polyubiquitinated proteins to promyelocytic leukemia bodies. J. Biol. Chem. 285(8), 5941–5953. doi: 10.1074/jbc.M109.039925
  61. Banani S.F., Lee H.O., Hyman A.A., Rosen M.K. (2017) Biomolecular condensates: organizers of cellular biochemistry. Nat. Rev. Mol. Cell Biol. 18(5), 285–298. doi: 10.1038/nrm.2017.7
  62. Shin Y., Brangwynne C.P. (2017) Liquid phase condensation in cell physiology and disease. Science. 357(6357), eaaf4382. doi: 10.1126/science.aaf4382
  63. Brangwynne C.P., Eckmann C.R., Courson D.S., Rybarska A., Hoege C., Gharakhani J., Jülicher F., Hyman A.A. (2009) Germline P granules ARE liquid droplets that localize by controlled dissolution/condensation. Science. 324, 1729–1732. doi: 10.1126/science.1172046
  64. Li P., Banjade S., Cheng H.C., Kim S., Chen B., Guo L., Llaguno M., Hollingsworth J.V., King D.S., Banani S.F., Russo P.S., Jiang Q.X., Nixon B.T., Rosen M.K. (2012) Phase transitions in the assembly of multivalent signalling proteins. Nature. 483(7389), 336–340. doi: 10.1038/nature10879
  65. Park S., Han S., Choi I., Kim B., Park S.P., Joe E.H., Suh Y.H. (2016) Interplay between leucine-rich repeat kinase 2 (LRRK2) and p62/SQSTM-1 in selective autophagy. PLoS One. 11(9), e0163029. doi: 10.1371/journal.pone.0163029
  66. Kurusu R., Morishita H., Komatsu M. (2024) p62 bodies: cytosolic zoning by phase separation. J. Biochem. 175(2), 141–146. doi: 10.1093/jb/mvad089
  67. Jiang T., Harder B., Rojo de la Vega M., Wong P.K., Chapman E., Zhang D.D. (2015) p62 links autophagy and Nrf2 signaling. Free Radic. Biol. Med. 88(Pt. B), 199–204. doi: 10.1016/j.freeradbiomed.2015.06.014
  68. Rhee S.G., Bae S.H. (2015) The antioxidant function of sestrins is mediated by promotion of autophagic degradation of Keap1 and Nrf2 activation and by inhibition of mTORC1. Free Radic. Biol. Med. 88(Pt. B), 205–211. doi: 10.1016/j.freeradbiomed.2015.06.007
  69. Ro S.H., Fay J., Cyuzuzo C.I., Jang Y., Lee N., Song H.S. Harris E.N. (2020) SESTRINs: emerging dynamic stress-sensors in metabolic and environmental health. Front. Cell Dev. Biol. 8, 603421. doi: 10.3389/fcell.2020.603421
  70. Bae S.H., Sung S.H., Oh S. Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., Kang D., Rhee S.G. (2013) Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 prevent oxidative liver damage. Cell Metab. 17(1), 73–84. doi: 10.1016/j.cmet.2012.12.002
  71. Kovaleva I.E., Tokarchuk A.V., Zheltukhin A.O., Dalina A.A., Safronov G.G., Evstafieva A.G., Lyamzaev K.G., Chumakov P.M., Budanov A.V. (2020) Mitochondrial localization of Sesn2. PLoS One. 15(4), e0226862. doi: 10.1371/journal.pone.0226862
  72. Gong L., Wang Z., Wang Z., Zhang Z. (2021) Sestrin2 as a potential target for regulating metabolic-related diseases. Front. Endocrinol. (Lausanne). 12, 751020. doi: 10.3389/fendo.2021.751020
  73. Fatima M.T., Hasan M., Abdelsalam S.S., Sivaraman S.K., El-Gamal H., Zahid M.A., Elrayess M.A., Korashy H.M., Zeidan A., Parray A.S., Agouni A. (2021) Sestrin2 suppression aggravates oxidative stress and apoptosis in endothelial cells subjected to pharmacologically induced endoplasmic reticulum stress. Eur. J. Pharmacol. 907, 174247. doi: 10.1016/j.ejphar.2021.174247
  74. Joo M.S., Kim W.D., Lee K.Y., Kim J.H., Koo J.H., Kim S.G. (2016) AMPK facilitates nuclear accumulation of Nrf2 by phosphorylating at serine 550. Mol. Cell. Biol. 36, 1931–1942. doi: 10.1128/MCB.00118-16
  75. Mo C., Wang L., Zhang J., Numazawa S., Tang H., Tang X., Han X., Li J., Yang M., Wang Z., Wei D., Xiao H. (2014) The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxid. Redox Signal. 20, 574–588. doi: 10.1089/ars.2012.5116
  76. Herzig S., Shaw R.J. (2018) AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat. Rev. Mol. Cell Biol. 19, 121–135. doi: 10.1038/nrm.2017.95
  77. Morgunova G.V., Klebanov A.A. (2019) Age-related AMP-activated protein kinase alterations: from cellular energetics to longevity. Cell Biochem. Funct. 37(3), 169–176. doi: 10.1002/cbf.3384
  78. Shackelford D.B., Shaw R.J. (2009) The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat. Rev. Cancer. 9, 563–575, doi: 10.1038/nrc2676
  79. Li X., Tang X., Su J., Xu G., Zhao L., Qi Q. (2019) Involvement of E-cadherin/AMPK/mTOR axis in LKB1-induced sensitivity of non-small cell lung cancer to gambogic acid. Biochem. Pharmacol. 169, 113635. doi: 10.1016/j.bcp.2019.113635.72
  80. O´Neill E.J., Sze N.S.K., MacPherson R.E.K., Tsiani E. (2024) Carnosic acid against lung cancer: induction of autophagy and activation of Sestrin-2/LKB1/AMPK signalling. Int. J. Mol. Sci. 25(4), 1950. doi: 10.3390/ijms25041950
  81. Kim M.J., Bae S.H., Ryu J.C., Kwon Y., Oh J.H., Kwon J., Moon J.S., Kim K., Miyawaki A., Lee M.G., Shin J., Kim Y.S., Kim C.H., Ryter S.W., Choi A.M., Rhee S.G., Ryu J.H., Yoon J.H. (2016) SESN2/Sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy. 12(8), 1272–1291. doi: 10.1080/15548627.2016.1183081
  82. Tomasovic A., Kurrle N., Surun D., Heidler J., Husnjak K., Poser I., Schnutgen F., Scheibe S., Seimetz M., Jaksch P., Hyman A., Weissmann N., von Melchner H. (2015) Sestrin 2 protein regulates plateletderived growth factor receptor β (Pdgfrβ) expression by modulating proteasomal and Nrf2 transcription factor functions. J. Biol. Chem. 290(15), 9738–9752. doi: 10.1074/jbc.M114.632133
  83. Eid A.A., Lee D.Y., Roman L.J., Khazim K., Gorin Y. (2013) Sestrin 2 and AMPK connect hyperglycemia to Nox4-dependent endothelial nitric oxide synthase uncoupling and matrix protein expression. Mol. Cell. Biol. 33(17), 3439–3460. doi: 10.1128/MCB.00217-13
  84. Ichimura Y., Waguri S., Sou Y.-S., Kageyama S., Hasegawa J., Ishimura R., Saito T., Yang Y., Kouno T., Fukutomi T., Hoshii T., Hirao A., Takagi K., Mizushima T., Motohashi H., Lee M-S., Yoshimori T., Tanaka K., Yamamoto M., Komatsu M. (2013) Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Mol. Cell. 51(5), 618–631. doi: 10.1016/j.molcel.2013.08.003
  85. Hashimoto K., Simmons A.N., Kajino-Sakamoto R., Tsuji Y., Ninomiya-Tsuji J. (2016) TAK1 regulates the Nrf2 antioxidant system through modulating p62/SQSTM1. Antioxid. Redox Signal. 25, 953–964. doi: 10.1089/ars.2016.6663
  86. Ran D., Ma Y., Liu W., Luo T., Zheng J., Wang D., Song R., Zhao H., Zou H., Gu J., Yuan Y., Bian J., Liu Z. (2020) TGF-β-activated kinase 1 (TAK1) mediates cadmium-induced autophagy in osteoblasts via the AMPK/mTORC1/ULK1 pathway. Toxicology. 442, 152538. doi: 10.1016/j.tox.2020.152538
  87. Duleh S., Wang X., Komirenko A., Margeta M. (2016) Activation of the Keap1/Nrf2 stress response pathway in autophagic vacuolar myopathies. Acta Neuropathol. Commun. 4(1), 115. doi: 10.1186/s40478-016-0384-6
  88. Yang Y., Willis T.L., Button R.W., Strang C.J., Fu Y., Wen X., Grayson P.R.C., Evans T., Sipthorpe R.J., Roberts S.L., Hu B., Zhang J., Lu B., Luo S. (2019) Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response. Nat. Commun. 10(1), 3759. doi: 10.1038/s41467-019-11671-2.19
  89. Goode A., Rea S., Sultana M., Shaw B., Searle M.S., Layfield R. (2016) ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling. Mol. Cell. Neurosci. 76, 52–58. 10.1016/j.mcn.2016.08.004
  90. Rolland T., Taşan M., Charloteaux B., Pevzner S.J., Zhong Q., Sahni N., Yi S., Lemmens I., Fontanillo C., Mosca R., Kamburov A., Ghiassian S.D., Yang X., Ghamsari L., Balcha D., Begg B.E., Braun P., Brehme M., Broly M.P., Carvunis A.-R., Convery-Zupan D., Corominas R., Coulombe-Huntington J., Dann E., Dreze M., Dricot A., Fan C., Franzosa E., Gebreab F., Gutierrez B.J., Hardy M.F., Jin M., Kang S., Kiros R., Lin G.N., Luck K., MacWilliams A., Menche J., Murray R.R., Palagi A., Poulin M.M., Rambout X., Rasla J., Reichert P., Romero V., Ruyssinck E., Sahalie J.M., Scholz A., Shah A.A., Sharma A., Shen Y., Spirohn K., Tam S., Tejeda A.O., Trigg S.A., Twizere J.-C., Vega K., Walsh J., Cusick M.E., Xia Y., Barabási A. L., Iakoucheva L.M., Aloy P., De Las Rivas J., Tavernier J., Calderwood M.A., Hill D.E., Hao T., Roth F.P., Vidal M. (2014) A proteome-scale map of the human interactome network. Cell. 159, 1212–1226. doi: 10.1016/j.cell.2014.10.050
  91. Seth D., Hess D.T., Hausladen A., Wang L., Wang Y.-J., Stamler J.S. (2018) A multiplex enzymatic machinery for cellular protein S-nitrosylation. Mol. Cell. 69, 451–464.e6. doi: 10.1016/j.molcel.2017.12.025
  92. Bonnet L.V., Palandri A., Flores-Martin J.B., Hallak M.E. (2024) Arginyltransferase 1 modulates p62-driven autophagy via mTORC1/AMPK signaling. Cell Commun. Signal. 22(1), 87. doi: 10.1186/s12964-024-01499-9
  93. Ji C.H., Kwon Y.T. (2017) Crosstalk and interplay between the ubiquitin-proteasome system and autophagy. Mol. Cells. 40(7), 441–449. doi: 10.14348/molcells.2017.0115
  94. Lee S.J., Kim H.Y., Lee M.J., Kim S.B., Kwon Y.T., Ji C.H. (2023) Characterization and chemical modulation of p62/SQSTM1/Sequestosome-1 as an autophagic N-recognin. Methods Enzymol. 686, 235–265. doi: 10.1016/bs.mie.2023.02.005
  95. Zhang Y., Mun S.R., Linares J.F., Ahn J., Towers C.G., Ji C.H., Fitzwalter B.E., Holden M.R., Mi W., Shi X., Moscat J., Thorburn A., Diaz-Meco M.T., Kwon Y.T., Kutateladze T.G. (2018) ZZ-dependent regulation of p62/SQSTM1 in autophagy. Nat. Commun. 9(1), 4373. doi: 10.1038/s41467-018-06878-8
  96. Cha-Molstad H., Yu J.E., Feng Z., Lee S.H., Kim J.G., Yang P., Han B., Sung K.W., Yoo Y.D., Hwang J., McGuire T., Shim S.M., Song H.D., Ganipisetti S., Wang N., Jang J.M., Lee M.J., Kim S.J., Lee K.H., Hong J.T., Ciechanover A., Mook-Jung I., Kim K.P., Xie X.Q., Kwon Y.T., Kim B.Y. (2017) p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis. Nat. Commun. 8(1), 102. doi: 10.1038/s41467-017-00085-7
  97. Demishtein A., Fraiberg M., Berko D., Tirosh B., Elazar Z., Navon A. (2017) SQSTM1/p62-mediated autophagy compensates for loss of proteasome polyubiquitin recruiting capacity. Autophagy. 13(10), 1697–1708. doi: 10.1080/15548627.2017.1356549
  98. Jung E.J., Sung K.W., Bae T.H., Kim H.Y., Choi H.R., Kim S.H., Jung C.H., Mun S.R., Son Y.S., Kim S., Suh Y.H., Kashina A., Park J.W., Kwon Y.T. (2023) The N-degron pathway mediates lipophagy: the chemical modulation of lipophagy in obesity and NAFLD. Metabolism. 146, 155644. doi: 10.1016/j.metabol.2023.155644
  99. Yoon M.J., Choi B., Kim E.J., Ohk J., Yang C., Choi Y.G., Lee J., Kang C., Song H.K., Kim Y.K., Woo J.S., Cho Y., Choi E.J., Jung H., Kim C. (2021) UXT chaperone prevents proteotoxicity acting as an autophagy adaptor for p62-dependent aggrephagy. Nat. Commun. 12(1), 1955. doi: 10.1038/s41467-021-22252-7
  100. Pan M., Yin Y., Hu T, Wang X., Jia T., Sun J., Wang Q., Meng W., Zhu J., Dai C., Hu H., Wang C. (2023) UXT attenuates the CGAS-STING1 signaling by targeting STING1 for autophagic degradation. Autophagy. 19(2), 440–456. doi: 10.1080/15548627.2022.2076192
  101. Han P., Mo S., Wang Z., Xu J., Fu X., Tian Y. (2023) UXT at the crossroads of cell death, immunity and neurodegenerative diseases. Front. Oncol. 13, 1179947. doi: 10.3389/fonc.2023.1179947
  102. Sun S., Tang Y., Lou X., Zhu L., Yang K., Zhang B., Shi H., Wang C. (2007) UXT is a novel and essential cofactor in the NF-κB transcriptional enhanceosome. J. Cell Biol. 178(2), 231–244. doi: 10.1083/jcb.200611081
  103. Sarkar S., Rubinsztein D.C. (2008) Small molecule enhancers of autophagy for neurodegenerative diseases. Mol. BioSyst. 4(9), 895–901. doi: 10.1039/b804606a
  104. Mizunoe Y., Kobayashi M., Sudo Y., Watanabe S., Yasukawa H., Natori D., Hoshino A., Negishi A., Okita N., Komatsu M., Higami Y. (2018) Trehalose protects against oxidative stress by regulating the Keap1-Nrf2 and autophagy pathways. Redox Biol. 15, 115–124. doi: 10.1016/j.redox.2017.09.007
  105. Galati S., Boni C., Gerra M.C., Lazzaretti M., Buschini A. (2019) Autophagy: a player in response to oxidative stress and DNA damage. Oxid. Med. Cell. Longev. 2019, 5692958. doi: 10.1155/2019/5692958
  106. Beese C.J., Brynjólfsdóttir S.H., Frankel L.B. (2020) Selective autophagy of the protein homeostasis machinery: ribophagy, proteaphagy and ER-phagy. Front. Cell Dev. Biol. 7, 373. doi: 10.3389/fcell.2019.00373
  107. Kim J., Lee S., Kim H., Lee H., Seong K.M., Youn H., Youn B. (2021) Autophagic organelles in DNA damage response. Front. Cell Dev. Biol. 9, 668735. doi: 10.3389/fcell.2021.668735
  108. Jadiya P., Tomar D. (2020) Mitochondrial protein quality control mechanisms. Genes (Basel). 11(5), 563. doi: 10.3390/genes11050563
  109. Rödl S., Herrmann J.M. (2023) The role of the proteasome in mitochondrial protein quality control. IUBMB Life. 75(10), 868–879. doi: 10.1002/iub.2734
  110. Gureev A.P., Shaforostova E.A., Popov V.N. (2019) Regulation of mitochondrial biogenesis as a way for active longevity: interaction between the Nrf2 and PGC-1α signaling pathways. Front. Genet. 10, 435. doi: 10.3389/fgene.2019.00435
  111. Gureev A.P., Sadovnikova I.S., Starkov N.N., Starkov A.A., Popov V.N. (2020) p62-Nrf2-p62 mitophagy regulatory loop as a target for preventive therapy of neurodegenerative diseases. Brain Sci. 10(11), 847. doi: 10.3390/brainsci10110847
  112. Шиловский Г.А., Ашапкин В.В. (2022) Транскрипционный фактор Nrf2 и митохондрии – друзья или противники в редокс-регуляции темпов старения. Биохимия. 87(12), 1856–1867. doi: 10.31857/S0320972522120065
  113. Redza-Dutordoir M., Averill-Bates D.A. (2021) Interactions between reactive oxygen species and autophagy: Special issue: Death mechanisms in cellular homeostasis. Biochim. Biophys. Acta Mol. Cell. Res. 1868(8), 119041. doi: 10.1016/j.bbamcr.2021.119041
  114. Lu C., Jiang Y., Xu W., Bao X. (2023) Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases. Cell Death Dis. 14(2), 160. doi: 10.1038/s41419-023-05669-4
  115. Далина А.А., Ковалева И.Е., Буданов А.В. (2018) Cестрины – шлагбаумы на путях от стресса к старению и болезням. Молекуляр. биология. 52(6), 948–962. doi: 10.1134/S0026898418060046
  116. Haidurov A., Budanov A.V. (2020) Sestrin family – the stem controlling healthy ageing. Mech. Ageing Dev. 192, 111379. doi: 10.1016/j.mad.2020.111379
  117. Ma S., Attarwala I.Y., Xie X.Q. (2019) SQSTM1/p62: a potential target for neurodegenerative disease. ACS Chem. Neurosci. 10, 2094–2114. doi: 10.1021/acschemneuro.8b00516
  118. Ramesh Babu J., Lamar Seibenhener M., Peng J., Strom A.L., Kemppainen R., Cox N., Zhu H., Wooten M.C., Diaz-Meco M.T., Moscat J., Wooten M.W. (2008) Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration. J. Neurochem. 106(1), 107–120. doi: 10.1111/j.1471-4159.2008.05340.x
  119. Zheng X., Wang W., Liu R., Huang H., Zhang R., Sun L. (2012) Effect of p62 on tau hyperphosphorylation in a rat model of Alzheimer´s disease. Neural Regen. Res. 7, 1304–1311. doi: 10.3969/j.issn.1673-5374.2012.17.004
  120. Caccamo A., Ferreira E., Branca C., Oddo S. (2017) p62 improves AD-like pathology by increasing autophagy. Mol. Psychiatry. 22, 865–873. doi: 10.1038/mp.2016.139
  121. Katsuragi Y., Ichimura Y., Komatsu M. (2016) Regulation of the Keap1–Nrf2 pathway by p62/SQSTM1. Curr. Opin. Toxicol. 1, 54–61. doi: 10.1016/j.cotox.2016.09.005
  122. Saito T., Ichimura Y., Taguchi K., Suzuki T., Mizushima T., Takagi K., Hirose Y., Nagahashi M., Iso T., Fukutomi T., Iso T., Fukutomi T., Ohishi M., Endo K., Uemura T., Nishito Y., Okuda S., Obata M., Kouno T., Imamura R., Tada Y., Obata R., Yasuda D., Takahashi K., Fujimura T., Pi J., Lee M.S., Ueno T., Ohe T., Mashino T., Wakai T., Kojima H., Okabe T., Nagano T., Motohashi H., Waguri S., Soga T., Yamamoto M., Tanaka K., Komatsu M. (2016) p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming. Nat. Commun. 7, 12030. doi: 10.1038/ncomms12030
  123. Menegon S., Columbano A., Giordano S. (2016) The dual roles of Nrf2 in cancer. Trends Mol. Med. 22, 578–593. doi: 10.1016/j.molmed.2016.05.002
  124. Ahmed S.M., Luo L., Namani A., Wang X.J., Tang X. (2017) Nrf2 signaling pathway: pivotal roles in inflammation. Biochim. Biophys. Acta Mol. Basis Dis. 1863, 585–597. doi: 10.1016/j.bbadis.2016.11.005
  125. Hennig P., Di Filippo M., Bilfeld G., Mellett M., Beer H.D. (2022) High p62 expression suppresses the NLRP1 inflammasome and increases stress resistance in cutaneous SCC cells. Cell Death Dis. 13(12), 1077. doi: 10.1038/s41419-022-05530-0
  126. Jeong S.J., Zhang X., Rodriguez-Velez A., Evans T.D., Razani B. (2019) p62/SQSTM1 and selective autophagy in cardiometabolic diseases. Antioxid. Redox Signal. 31(6), 458–471. doi: 10.1089/ars.2018.7649
  127. Davidson J.M., Chung R.S., Lee A. (2022) The converging roles of sequestosome-1/p62 in the molecular pathways of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Neurobiol. Dis. 166, 105653. doi: 10.1016/j.nbd.2022.105653
  128. Jiang B., Zhou X., Yang T., Wang L., Feng L., Wang Z., Xu J., Jing W., Wang T., Su H., Yang G., Zhang Z. (2023) The role of autophagy in cardiovascular disease: cross-interference of signaling pathways and underlying therapeutic targets. Front. Cardiovasc. Med. 10, 1088575. doi: 10.3389/fcvm.2023.1088575
  129. Tan C.T., Soh N.J.H., Chang H.C., Yu V.C. (2023) p62/SQSTM1 in liver diseases: the usual suspect with multifarious identities. FEBS J. 290(4), 892–912. doi: 10.1111/febs.16317
  130. Yang H., Ni H.M., Ding W.X. (2019) Emerging players in autophagy deficiency-induced liver injury and tumorigenesis. Gene Exp. 19(3), 229–234. doi: 10.3727/105221619X15486875608177
  131. Yu M., Zhang H., Wang B., Zhang Y., Zheng X., Shao B., Zhuge Q., Jin K. (2021) Key signaling pathways in aging and potential interventions for healthy aging. Cells. 10(3), 660. doi: 10.3390/cells10030660
  132. Si J., Liu B., Qi K., Chen X., Li D., Yang S., Ji E. (2023) Tanshinone IIA inhibited intermittent hypoxia induced neuronal injury through promoting autophagy via AMPK-mTOR signaling pathway. J. Ethnopharmacol. 315, 116677. doi: 10.1016/j.jep.2023.116677

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Structural organization of the p62 protein. Domain structure of the human p62 protein (440 aa): 21–103 aa – PB1 domain (contains Phox and Bem1p motifs); 128–163 aa – ZZ-type zinc finger domain (ZZ); 225–250 aa – TRAF6-binding domain TB; 321–341 aa – LC3-interacting domain (LIR); 346–359 aa – KEAP1-interacting domain KIR (K); 386–440 aa – ubiquitin-binding domain (UBA).

Download (62KB)
Indexing metadata
3. Fig. 2. NRF2 regulatory pathways in mitophagy and autophagy. A simplified diagram is shown consisting of a regulatory loop including p62, KEAP1 and NRF2, and another regulatory loop including AMPK (5´-AMP-activated protein kinase), SESN2 (sestrin 2), ULK1 (UNC-51-like autophagy activating kinase 1). Arrowheads indicate direct stimulatory effects including catalysis; blunted lines indicate inhibitory/suppressive effects on NRF2 activity/expression.

Download (66KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».