Sestrins in Physiological Stress Responses

Literature Cited

1. 1. 

   Sohal RS. 2002. Oxidative stress hypothesis of aging. Free Radic. Biol. Med. 33:573–74
   [Google Scholar]
2. 2. 

   Golden TR, Hinerfeld DA, Melov S 2002. Oxidative stress and aging: beyond correlation. Aging Cell 1:117–23
   [Google Scholar]
3. 3. 

   Epel ES, Lithgow GJ. 2014. Stress biology and aging mechanisms: toward understanding the deep connection between adaptation to stress and longevity. J. Gerontol. A Biol. Sci. Med. Sci. 69:Suppl. 1S10–16
   [Google Scholar]
4. 4. 

   Miller RA. 2009. Cell stress and aging: new emphasis on multiplex resistance mechanisms. J. Gerontol. A Biol. Sci. Med. Sci. 64:179–82
   [Google Scholar]
5. 5. 

   Velasco-Miguel S, Buckbinder L, Jean P, Gelbert L, Talbott R et al. 1999. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene 18:127–37
   [Google Scholar]
6. 6. 

   Buckbinder L, Talbott R, Seizinger BR, Kley N 1994. Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes. PNAS 91:10640–44
   [Google Scholar]
7. 7. 

   Budanov AV, Shoshani T, Faerman A, Zelin E, Kamer I et al. 2002. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 21:6017–31
   [Google Scholar]
8. 8. 

   Budanov AV, Karin M. 2008. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134:451–60
   [Google Scholar]
9. 9. 

   Maiuri MC, Malik SA, Morselli E, Kepp O, Criollo A et al. 2009. Stimulation of autophagy by the p53 target gene Sestrin2. Cell Cycle 8:1571–76
   [Google Scholar]
10. 10. 

    Lee JH, Budanov AV, Park EJ, Birse R, Kim TE et al. 2010. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327:1223–28
    [Google Scholar]
11. 11. 

    Yang YL, Loh KS, Liou BY, Chu IH, Kuo CJ et al. 2013. SESN-1 is a positive regulator of lifespan in Caenorhabditiselegans. Exp. . Gerontol 48:371–79
    [Google Scholar]
12. 12. 

    Rafia S, Saran S. 2019. Sestrin-like protein from Dictyosteliumdiscoideum is involved in autophagy under starvation stress. Microbiol. Res. 220:61–71
    [Google Scholar]
13. 13. 

    Chen CC, Jeon SM, Bhaskar PT, Nogueira V, Sundararajan D et al. 2010. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev. Cell 18:592–604
    [Google Scholar]
14. 14. 

    Shin BY, Jin SH, Cho IJ, Ki SH 2012. Nrf2-ARE pathway regulates induction of Sestrin-2 expression. Free Radic. Biol. Med. 53:834–41
    [Google Scholar]
15. 15. 

    Kim MG, Yang JH, Kim KM, Jang CH, Jung JY et al. 2015. Regulation of Toll-like receptor-mediated Sestrin2 induction by AP-1, Nrf2, and the ubiquitin-proteasome system in macrophages. Toxicol. Sci. 144:425–35
    [Google Scholar]
16. 16. 

    Parmigiani A, Budanov AV. 2016. Sensing the environment through sestrins: implications for cellular metabolism. Int. Rev. Cell Mol. Biol. 327:1–42
    [Google Scholar]
17. 17. 

    Bruning A, Rahmeh M, Friese K 2013. Nelfinavir and bortezomib inhibit mTOR activity via ATF4-mediated sestrin-2 regulation. Mol. Oncol. 7:1012–18
    [Google Scholar]
18. 18. 

    Park HW, Park H, Ro SH, Jang I, Semple IA et al. 2014. Hepatoprotective role of Sestrin2 against chronic ER stress. Nat. Commun. 5:4233
    [Google Scholar]
19. 19. 

    Misiewicz M, Dery MA, Foveau B, Jodoin J, Ruths D, Leblanc AC 2013. Identification of a novel endoplasmic reticulum stress response element regulated by XBP1. J. Biol. Chem. 288:20378–91
    [Google Scholar]
20. 20. 

    Saveljeva S, Cleary P, Mnich K, Ayo A, Pakos-Zebrucka K et al. 2016. Endoplasmic reticulum stress-mediated induction of SESTRIN 2 potentiates cell survival. Oncotarget 7:12254–66
    [Google Scholar]
21. 21. 

    Jegal KH, Park SM, Cho SS, Byun SH, Ku SK et al. 2017. Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury. Biochim. Biophys. Acta Mol. Cell Res. 1864:1295–307
    [Google Scholar]
22. 22. 

    Ben-Sahra I, Dirat B, Laurent K, Puissant A, Auberger P et al. 2013. Sestrin2 integrates Akt and mTOR signaling to protect cells against energetic stress-induced death. Cell Death Differ 20:611–19
    [Google Scholar]
23. 23. 

    Ding B, Parmigiani A, Divakaruni AS, Archer K, Murphy AN, Budanov AV 2016. Sestrin2 is induced by glucose starvation via the unfolded protein response and protects cells from non-canonical necroptotic cell death. Sci. Rep. 6:22538
    [Google Scholar]
24. 24. 

    Garaeva AA, Kovaleva IE, Chumakov PM, Evstafieva AG 2016. Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4. Cell Cycle 15:64–71
    [Google Scholar]
25. 25. 

    Ye J, Palm W, Peng M, King B, Lindsten T et al. 2015. GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev 29:2331–36
    [Google Scholar]
26. 26. 

    Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME et al. 2016. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science 351:53–58
    [Google Scholar]
27. 27. 

    Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM et al. 2016. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351:43–48
    [Google Scholar]
28. 28. 

    Kimball SR, Gordon BS, Moyer JE, Dennis MD, Jefferson LS 2016. Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation. Cell Signal 28:896–906
    [Google Scholar]
29. 29. 

    Zhang XY, Wu XQ, Deng R, Sun T, Feng GK, Zhu XF 2013. Upregulation of sestrin 2 expression via JNK pathway activation contributes to autophagy induction in cancer cells. Cell Signal 25:150–58
    [Google Scholar]
30. 30. 

    Lee JH, Budanov AV, Talukdar S, Park EJ, Park H et al. 2012. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab 16:311–21
    [Google Scholar]
31. 31. 

    Chai D, Wang G, Zhou Z, Yang H, Yu Z 2015. Insulin increases Sestrin 2 content by reducing its degradation through the PI₃K/mTOR signaling pathway. Int. J. Endocrinol. 2015:505849
    [Google Scholar]
32. 32. 

    Kumar A, Shaha C. 2018. RBX1-mediated ubiquitination of SESN2 promotes cell death upon prolonged mitochondrial damage in SH-SY5Y neuroblastoma cells. Mol. Cell. Biochem. 446:1–9
    [Google Scholar]
33. 33. 

    Lear TB, Lockwood KC, Ouyang Y, Evankovich JW, Larsen MB et al. 2019. The RING-type E3 ligase RNF186 ubiquitinates Sestrin-2 and thereby controls nutrient sensing. J. Biol. Chem. 294:16527–34
    [Google Scholar]
34. 34. 

    Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM 2004. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science 304:596–600
    [Google Scholar]
35. 35. 

    Kim H, An S, Ro SH, Teixeira F, Park GJ et al. 2015. Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains. Nat. Commun. 6:10025
    [Google Scholar]
36. 36. 

    Bae SH, Sung SH, Oh SY, Lim JM, Lee SK et al. 2013. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab 17:73–84
    [Google Scholar]
37. 37. 

    Ro SH, Semple IA, Park H, Park H, Park HW et al. 2014. Sestrin2 promotes Unc-51-like kinase 1 (ULK1)-mediated phosphorylation of p62/sequestosome-1. FEBS J 281:3816–27
    [Google Scholar]
38. 38. 

    Jain A, Lamark T, Sjottem E, Larsen KB, Awuh JA 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. 285:22576–91
    [Google Scholar]
39. 39. 

    Sanli T, Linher-Melville K, Tsakiridis T, Singh G 2012. Sestrin2 modulates AMPK subunit expression and its response to ionizing radiation in breast cancer cells. PLOS ONE 7:e32035
    [Google Scholar]
40. 40. 

    Liu X, Niu Y, Yuan H, Huang J, Fu L 2015. AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy. Metabolism 64:658–65
    [Google Scholar]
41. 41. 

    Morrison A, Chen L, Wang J, Zhang M, Yang H et al. 2015. Sestrin2 promotes LKB1-mediated AMPK activation in the ischemic heart. FASEB J 29:408–17
    [Google Scholar]
42. 42. 

    Peng M, Yin N, Li MO 2014. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell 159:122–33
    [Google Scholar]
43. 43. 

    Kim JS, Ro SH, Kim M, Park HW, Semple IA et al. 2015. Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci. Rep. 5:9502
    [Google Scholar]
44. 44. 

    Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim YC et al. 2014. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep 9:1281–91
    [Google Scholar]
45. 45. 

    Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, Scaria SM et al. 2014. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep 9:1–8
    [Google Scholar]
46. 46. 

    Kowalsky AH, Namkoong S, Mettetal E, Park HW, Kazyken D et al. 2020. The GATOR2-mTORC2 axis mediates Sestrin2-induced AKT Ser/Thr kinase activation. J. Biol. Chem. 295:1769–80
    [Google Scholar]
47. 47. 

    Tao R, Xiong X, Liangpunsakul S, Dong XC 2015. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes 64:1211–23
    [Google Scholar]
48. 48. 

    Byun JK, Choi YK, Kim JH, Jeong JY, Jeon HJ et al. 2017. A positive feedback loop between Sestrin2 and mTORC2 is required for the survival of glutamine-depleted lung cancer cells. Cell Rep 20:586–99
    [Google Scholar]
49. 49. 

    Huang M, Kim HG, Zhong X, Dong C, Zhang B et al. 2019. Sestrin 3 protects against diet-induced nonalcoholic steatohepatitis in mice through suppression of transforming growth factor β signal transduction. Hepatology 71:76–92
    [Google Scholar]
50. 50. 

    Wempe F, De-Zolt S, Koli K, Bangsow T, Parajuli N et al. 2010. Inactivation of sestrin 2 induces TGF-β signaling and partially rescues pulmonary emphysema in a mouse model of COPD. Dis. Model. Mech. 3:246–53
    [Google Scholar]
51. 51. 

    Yang JH, Kim KM, Cho SS, Shin SM, Ka SO et al. 2019. Inhibitory effect of Sestrin 2 on hepatic stellate cell activation and liver fibrosis. Antioxid. Redox Signal. 31:243–59
    [Google Scholar]
52. 52. 

    Ding B, Parmigiani A, Yang C, Budanov AV 2015. Sestrin2 facilitates death receptor-induced apoptosis in lung adenocarcinoma cells through regulation of XIAP degradation. Cell Cycle 14:3231–41
    [Google Scholar]
53. 53. 

    Ho A, Cho CS, Namkoong S, Cho US, Lee JH 2016. Biochemical basis of sestrin physiological activities. Trends Biochem. Sci. 41:621–32
    [Google Scholar]
54. 54. 

    Søndergaard L. 1993. Homology between the mammalian liver and the Drosophila fat body. Trends Genet 9:193
    [Google Scholar]
55. 55. 

    Budanov AV, Lee JH, Karin M 2010. Stressin’ Sestrins take an aging fight. EMBO Mol. Med. 2:388–400
    [Google Scholar]
56. 56. 

    Kim M, Sujkowski A, Namkoong S, Gu B, Cobb T et al. 2020. Sestrin is an evolutionarily conserved mediator of exercise. Nat. Commun. 11:190
    [Google Scholar]
57. 57. 

    Peeters H, Debeer P, Bairoch A, Wilquet V, Huysmans C et al. 2003. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. Hum. Genet. 112:573–80
    [Google Scholar]
58. 58. 

    Angulo P. 2002. Nonalcoholic fatty liver disease. N. Engl. J. Med. 346:1221–31
    [Google Scholar]
59. 59. 

    Wu J, Liu J, Waalkes MP, Cheng ML, Li L et al. 2008. High dietary fat exacerbates arsenic-induced liver fibrosis in mice. Exp. Biol. Med. 233:377–84
    [Google Scholar]
60. 60. 

    Saxena NK, Ikeda K, Rockey DC, Friedman SL, Anania FA 2002. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology 35:762–71
    [Google Scholar]
61. 61. 

    Pagliassotti MJ. 2012. Endoplasmic reticulum stress in nonalcoholic fatty liver disease. Annu. Rev. Nutr. 32:17–33
    [Google Scholar]
62. 62. 

    Jin SH, Yang JH, Shin BY, Seo K, Shin SM et al. 2013. Resveratrol inhibits LXRα-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction. Toxicol. Appl. Pharmacol. 271:95–105
    [Google Scholar]
63. 63. 

    Hariri N, Gougeon R, Thibault L 2010. A highly saturated fat-rich diet is more obesogenic than diets with lower saturated fat content. Nutr. Res. 30:632–43
    [Google Scholar]
64. 64. 

    Fu S, Yang L, Li P, Hofmann O, Dicker L et al. 2011. Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 473:528–31
    [Google Scholar]
65. 65. 

    Zhang K, Wang S, Malhotra J, Hassler JR, Back SH et al. 2011. The unfolded protein response transducer IRE1α prevents ER stress-induced hepatic steatosis. EMBO J 30:1357–75
    [Google Scholar]
66. 66. 

    Han J, Kaufman RJ. 2016. The role of ER stress in lipid metabolism and lipotoxicity. J. Lipid. Res. 57:1329–38
    [Google Scholar]
67. 67. 

    Li Z, Votava JA, Zajac GJM, Nguyen JN, Leyva Jaimes FB et al. 2020. Integrating mouse and human genetic data to move beyond GWAS and identify causal genes in cholesterol metabolism. Cell Metab 31:741–54.e5
    [Google Scholar]
68. 68. 

    Kim HJ, Joe Y, Kim SK, Park SU, Park J et al. 2017. Carbon monoxide protects against hepatic steatosis in mice by inducing sestrin-2 via the PERK-eIF2α-ATF4 pathway. Free Radic. Biol. Med. 110:81–91
    [Google Scholar]
69. 69. 

    Dooley S, ten Dijke P 2012. TGF-β in progression of liver disease. Cell Tissue Res 347:245–56
    [Google Scholar]
70. 70. 

    Liu Y, Kim HG, Dong E, Dong C, Huang M et al. 2019. Sesn3 deficiency promotes carcinogen-induced hepatocellular carcinoma via regulation of the hedgehog pathway. Biochim. Biophys. Acta Mol. Basis Dis. 1865:2685–93
    [Google Scholar]
71. 71. 

    Yang JH, Kim KM, Kim MG, Seo KH, Han JY et al. 2015. Role of sestrin2 in the regulation of proinflammatory signaling in macrophages. Free Radic. Biol. Med. 78:156–67
    [Google Scholar]
72. 72. 

    Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N 2016. Acetaminophen-induced hepatotoxicity: a comprehensive update. J. Clin. Transl. Hepatol. 4:131–42
    [Google Scholar]
73. 73. 

    Kim SJ, Kim KM, Yang JH, Cho SS, Kim JY et al. 2017. Sestrin2 protects against acetaminophen-induced liver injury. Chem. Biol. Interact. 269:50–58
    [Google Scholar]
74. 74. 

    Kumar A, Giri S, Shaha C 2018. Sestrin2 facilitates glutamine-dependent transcription of PGC-1α and survival of liver cancer cells under glucose limitation. FEBS J 285:1326–45
    [Google Scholar]
75. 75. 

    Yang WS, Stockwell BR. 2016. Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:165–76
    [Google Scholar]
76. 76. 

    Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED et al. 2014. Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 3:e02523
    [Google Scholar]
77. 77. 

    Dai J, Huang Q, Niu K, Wang B, Li Y et al. 2018. Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma. Cancer Med 7:5691–703
    [Google Scholar]
78. 78. 

    Park SJ, Cho SS, Kim KM, Yang JH, Kim JH et al. 2019. Protective effect of sestrin2 against iron overload and ferroptosis-induced liver injury. Toxicol. Appl. Pharmacol. 379:114665
    [Google Scholar]
79. 79. 

    Shin D, Kim EH, Lee J, Roh JL 2018. Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer. Free Radic. Biol. Med. 129:454–62
    [Google Scholar]
80. 80. 

    Cho CS, Kowalsky AH, Namkoong S, Park SR, Wu S et al. 2019. Concurrent activation of growth factor and nutrient arms of mTORC1 induces oxidative liver injury. Cell Discov 5:60
    [Google Scholar]
81. 81. 

    Crook MA, Hally V, Panteli JV 2001. The importance of the refeeding syndrome. Nutrition 17:632–37
    [Google Scholar]
82. 82. 

    Neinast M, Murashige D, Arany Z 2019. Branched chain amino acids. Annu. Rev. Physiol. 81:139–64
    [Google Scholar]
83. 83. 

    Sengupta S, Giaime E, Narayan S, Hahm S, Howell J et al. 2019. Discovery of NV-5138, the first selective brain mTORC1 activator. Sci. Rep. 9:4107
    [Google Scholar]
84. 84. 

    Segalés J, Perdiguero E, Serrano AL, Sousa-Victor P, Ortet L et al. 2020. Sestrin prevents muscle atrophy from disuse and aging by integrating anabolic and catabolic signals. Nat. Commun. 11:189
    [Google Scholar]
85. 85. 

    Cao Y, Yao Z, Sarkar D, Lawrence M, Sanchez GJ et al. 2010. Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev. Cell 18:662–74
    [Google Scholar]
86. 86. 

    Blum R, Vethantham V, Bowman C, Rudnicki M, Dynlacht BD 2012. Genome-wide identification of enhancers in skeletal muscle: the role of MyoD1. Genes Dev 26:2763–79
    [Google Scholar]
87. 87. 

    Cai B, Ma M, Chen B, Li Z, Abdalla BA et al. 2018. MiR-16–5p targets SESN1 to regulate the p53 signaling pathway, affecting myoblast proliferation and apoptosis, and is involved in myoblast differentiation. Cell Death Dis 9:367
    [Google Scholar]
88. 88. 

    Nascimento EB, Osler ME, Zierath JR 2013. Sestrin 3 regulation in type 2 diabetic patients and its influence on metabolism and differentiation in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 305:E1408–14
    [Google Scholar]
89. 89. 

    Hood DA, Memme JM, Oliveira AN, Triolo M 2019. Maintenance of skeletal muscle mitochondria in health, exercise, and aging. Annu. Rev. Physiol. 81:19–41
    [Google Scholar]
90. 90. 

    Merry TL, Ristow M. 2016. Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?. J. Physiol. 594:5135–47
    [Google Scholar]
91. 91. 

    Crisol BM, Lenhare L, Gaspar RS, Gaspar RC, Munoz VR et al. 2018. The role of physical exercise on Sestrin1 and 2 accumulations in the skeletal muscle of mice. Life Sci 194:98–103
    [Google Scholar]
92. 92. 

    Lenhare L, Crisol BM, Silva VRR, Katashima CK, Cordeiro AV et al. 2017. Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Exp. Gerontol. 97:17–21
    [Google Scholar]
93. 93. 

    Zeng N, D'Souza RF, Figueiredo VC, Markworth JF, Roberts LA et al. 2017. Acute resistance exercise induces Sestrin2 phosphorylation and p62 dephosphorylation in human skeletal muscle. Physiol. Rep. 5:e13526
    [Google Scholar]
94. 94. 

    Pillon NJ, Gabriel BM, Dollet L, Smith JAB, Puig LS et al. 2020. Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity. Nat. Commun. 11:470
    [Google Scholar]
95. 95. 

    Zeng N, D'Souza RF, Sorrenson B, Merry TL, Barnett MPG et al. 2018. The putative leucine sensor Sestrin2 is hyperphosphorylated by acute resistance exercise but not protein ingestion in human skeletal muscle. Eur. J. Appl. Physiol. 118:1241–53
    [Google Scholar]
96. 96. 

    Gao Y, Arfat Y, Wang H, Goswami N 2018. Muscle atrophy induced by mechanical unloading: mechanisms and potential countermeasures. Front. Physiol. 9:235
    [Google Scholar]
97. 97. 

    Zeng N, D'Souza RF, Mitchell CJ, Cameron-Smith D 2018. Sestrins are differentially expressed with age in the skeletal muscle of men: a cross-sectional analysis. Exp. Gerontol. 110:23–34
    [Google Scholar]
98. 98. 

    Sujkowski A, Wessells R. 2018. Using Drosophila to understand biochemical and behavioral responses to exercise. Exerc. Sport Sci. Rev. 46:112–20
    [Google Scholar]
99. 99. 

    Richter EA, Ruderman NB. 2009. AMPK and the biochemistry of exercise: implications for human health and disease. Biochem. J. 418:261–75
    [Google Scholar]
100. 100. 

     Sakamoto K, Aschenbach WG, Hirshman MF, Goodyear LJ 2003. Akt signaling in skeletal muscle: regulation by exercise and passive stretch. Am. J. Physiol. Endocrinol. Metab. 285:E1081–88
     [Google Scholar]
101. 101. 

     Escobar KA, Cole NH, Mermier CM, VanDusseldorp TA 2019. Autophagy and aging: maintaining the proteome through exercise and caloric restriction. Aging Cell 18:e12876
     [Google Scholar]
102. 102. 

     Kim MJ, Bae SH, Ryu JC, Kwon Y, Oh JH et al. 2016. SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy 12:1272–91
     [Google Scholar]
103. 103. 

     Kumar A, Shaha C. 2018. SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci. Rep. 8:615
     [Google Scholar]
104. 104. 

     Wang P, Wang L, Lu J, Hu Y, Wang Q et al. 2019. SESN2 protects against doxorubicin-induced cardiomyopathy via rescuing mitophagy and improving mitochondrial function. J. Mol. Cell. Cardiol. 133:125–37
     [Google Scholar]
105. 105. 

     Zong H, Ren JM, Young LH, Pypaert M, Mu J et al. 2002. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. PNAS 99:15983–87
     [Google Scholar]
106. 106. 

     Fortini P, Ferretti C, Iorio E, Cagnin M, Garribba L et al. 2016. The fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis. Cell Death Dis 7:e2168
     [Google Scholar]
107. 107. 

     Sin J, Andres AM, Taylor DJ, Weston T, Hiraumi Y et al. 2016. Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy 12:369–80
     [Google Scholar]
108. 108. 

     Lin Y, Zhao Y, Li R, Gong J, Zheng Y, Wang Y 2014. PGC-1α is associated with C2C12 myoblast differentiation. Cent. Eur. J. Biol. 9:1030–36
     [Google Scholar]
109. 109. 

     Zeltukhin AO, Ilyinskaya GV, Budanov AV, Chumakov PM 2018. Some phenotypic characteristics of nematode Caenorhabditiselegans strains with defective functions of the sestrin (cSesn) gene. Biomed. Pharmacol. J. 11: http://dx.doi.org/10.13005/bpj/1430
     [Crossref] [Google Scholar]
110. 110. 

     Kovaleva IE, Tokarchuk AV, Zheltukhin AO, Dalina AA, Safronov GG et al. 2020. Mitochondrial localization of SESN2. PLOS ONE 15:e0226862
     [Google Scholar]
111. 111. 

     Kim YC, Guan KL. 2015. mTOR: a pharmacologic target for autophagy regulation. J. Clin. Investig. 125:25–32
     [Google Scholar]
112. 112. 

     Li X, Monks B, Ge Q, Birnbaum MJ 2007. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1α transcription coactivator. Nature 447:1012–16
     [Google Scholar]
113. 113. 

     Sandri M, Lin J, Handschin C, Yang W, Arany ZP et al. 2006. PGC-1α protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. PNAS 103:16260–65
     [Google Scholar]
114. 114. 

     Ljubicic V, Jasmin BJ. 2013. AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy. Trends Mol. Med. 19:614–24
     [Google Scholar]
115. 115. 

     Kim MH, Kay DI, Rudra RT, Chen BM, Hsu N et al. 2011. Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice. Hum. Mol. Genet. 20:1324–38
     [Google Scholar]
116. 116. 

     Xu ZR, Tan ZJ, Zhang Q, Gui QF, Yang YM 2015. The effectiveness of leucine on muscle protein synthesis, lean body mass and leg lean mass accretion in older people: a systematic review and meta-analysis. Br. J. Nutr. 113:25–34
     [Google Scholar]
117. 117. 

     Makanae Y, Fujita S. 2015. Role of exercise and nutrition in the prevention of sarcopenia. J. Nutr. Sci. Vitaminol. 61:Suppl.S125–27
     [Google Scholar]
118. 118. 

     Deane CS, Wilkinson DJ, Phillips BE, Smith K, Etheridge T, Atherton PJ 2017. “Nutraceuticals” in relation to human skeletal muscle and exercise. Am. J. Physiol. Endocrinol. Metab. 312:E282–99
     [Google Scholar]
119. 119. 

     Rodgers JT, King KY, Brett JO, Cromie MJ, Charville GW et al. 2014. mTORC1 controls the adaptive transition of quiescent stem cells from G₀ to G_Alert. Nature 510:393–96
     [Google Scholar]
120. 120. 

     Garcia-Prat L, Martinez-Vicente M, Perdiguero E, Ortet L, Rodriguez-Ubreva J et al. 2016. Autophagy maintains stemness by preventing senescence. Nature 529:37–42
     [Google Scholar]
121. 121. 

     Bigarella CL, Liang R, Ghaffari S 2014. Stem cells and the impact of ROS signaling. Development 141:4206–18
     [Google Scholar]
122. 122. 

     Dalen JE, Alpert JS, Goldberg RJ, Weinstein RS 2014. The epidemic of the 20^th century: coronary heart disease. Am. J. Med. 127:807–12
     [Google Scholar]
123. 123. 

     Quan N, Sun W, Wang L, Chen X, Bogan JS et al. 2017. Sestrin2 prevents age-related intolerance to ischemia and reperfusion injury by modulating substrate metabolism. FASEB J 31:4153–67
     [Google Scholar]
124. 124. 

     Quan N, Wang L, Chen X, Luckett C, Cates C et al. 2018. Sestrin2 prevents age-related intolerance to post myocardial infarction via AMPK/PGC-1α pathway. J. Mol. Cell. Cardiol. 115:170–78
     [Google Scholar]
125. 125. 

     Ye J, Wang M, Xu Y, Liu J, Jiang H et al. 2017. Sestrins increase in patients with coronary artery disease and associate with the severity of coronary stenosis. Clin. Chim. Acta 472:51–57
     [Google Scholar]
126. 126. 

     Wang H, Li N, Shao X, Li J, Guo L et al. 2019. Increased plasma sestrin2 concentrations in patients with chronic heart failure and predicted the occurrence of major adverse cardiac events: a 36-month follow-up cohort study. Clin. Chim. Acta 495:338–44
     [Google Scholar]
127. 127. 

     Lip GY, Fauchier L, Freedman SB, Van Gelder I, Natale A et al. 2016. Atrial fibrillation. Nat. Rev. Dis. Primers 2:16016
     [Google Scholar]
128. 128. 

     Dong Z, Lin C, Liu Y, Jin H, Wu H et al. 2017. Upregulation of sestrins protect atriums against oxidative damage and fibrosis in human and experimental atrial fibrillation. Sci. Rep. 7:46307
     [Google Scholar]
129. 129. 

     Chiao YA, Rabinovitch PS. 2015. The aging heart. Cold Spring Harb. Perspect. Med. 5:a025148
     [Google Scholar]
130. 130. 

     Xue R, Zeng J, Chen Y, Chen C, Tan W et al. 2017. Sestrin 1 ameliorates cardiac hypertrophy via autophagy activation. J. Cell. Mol. Med. 21:1193–205
     [Google Scholar]
131. 131. 

     Sun X, Han F, Lu Q, Li X, Ren D et al. 2020. Empagliflozin ameliorates obesity-related cardiac dysfunction by regulating sestrin2-mediated AMPK-mTOR signaling and redox homeostasis in high-fat diet-induced obese mice. Diabetes 69:1292–305
     [Google Scholar]
132. 132. 

     Chatterjee K, Zhang J, Honbo N, Karliner JS 2010. Doxorubicin cardiomyopathy. Cardiology 115:155–62
     [Google Scholar]
133. 133. 

     Li R, Huang Y, Semple I, Kim M, Zhang Z, Lee JH 2019. Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity. Am. J. Physiol. Heart Circ. Physiol. 317:H39–48
     [Google Scholar]
134. 134. 

     Wang Z, Bu L, Yang P, Feng S, Xu F 2019. Alleviation of sepsis-induced cardiac dysfunction by overexpression of Sestrin2 is associated with inhibition of pS6K and activation of the p-AMPK pathway. Mol. Med. Rep. 20:2511–18
     [Google Scholar]
135. 135. 

     Yang K, Xu C, Zhang Y, He S, Li D 2017. Sestrin2 suppresses classically activated macrophages-mediated inflammatory response in myocardial infarction through inhibition of mTORC1 signaling. Front. Immunol. 8:728
     [Google Scholar]
136. 136. 

     Stokfisz K, Ledakowicz-Polak A, Zagorski M, Zielinska M 2017. Ischaemic preconditioning—current knowledge and potential future applications after 30 years of experience. Adv. Med. Sci. 62:307–16
     [Google Scholar]
137. 137. 

     Yan WJ, Dong HL, Xiong LZ 2013. The protective roles of autophagy in ischemic preconditioning. Acta Pharmacol. Sin. 34:636–43
     [Google Scholar]
138. 138. 

     Thompson PD. 2001. Exercise and Sports Cardiology New York: McGraw Hill
139. 139. 

     Marques-Aleixo I, Santos-Alves E, Oliveira PJ, Moreira PI, Magalhaes J, Ascensao A 2018. The beneficial role of exercise in mitigating doxorubicin-induced mitochondrionopathy. Biochim. Biophys. Acta Rev. Cancer 1869:189–99
     [Google Scholar]
140. 140. 

     Li L, Xiao L, Hou Y, He Q, Zhu J et al. 2016. Sestrin2 silencing exacerbates cerebral ischemia/reperfusion injury by decreasing mitochondrial biogenesis through the AMPK/PGC-1α pathway in rats. Sci. Rep. 6:30272
     [Google Scholar]
141. 141. 

     Ro SH, Xue X, Ramakrishnan SK, Cho CS, Namkoong S et al. 2016. Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis. eLife 5:12204
     [Google Scholar]
142. 142. 

     Mattson MP. 2008. Hormesis defined. Ageing Res. Rev. 7:1–7
     [Google Scholar]
143. 143. 

     Sanders CL. 2010. Radiation Hormesis and the Linear-No-Threshold Assumption New York: Springer
144. 144. 

     Rattan SI. 2004. Aging intervention, prevention, and therapy through hormesis. J. Gerontol. A Biol. Sci. Med. Sci. 59:705–9
     [Google Scholar]