SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity

Araujo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S. Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: What we need in the future. Liver Int. 2018;38:47–51. 10.1111/liv.13643

[2]

Angulo P. Nonalcoholic fatty liver disease. New Engl J Med. 2002;346:1221–31. 10.1056/nejmra011775

[3]

Gonzalez-Rodriguez A, Mayoral R, Agra N, Valdecantos MP, Pardo V, Miquilena-Colina ME, et al. Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD. Cell Death Dis. 2014;5:e1179. 10.1038/cddis.2014.162

[4]

Fukuo Y, Yamashina S, Sonoue H, Arakawa A, Nakadera E, Aoyama T, et al. Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease. Hepatol Res. 2014;44:1026–36. 10.1111/hepr.12282

[5]

Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, et al. Autophagy regulates lipid metabolism. Nature. 2009;458:1131–5. 10.1038/nature07976

[6]

Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy. 2011;7:279–96. 10.4161/auto.7.3.14487

[7]

Tsai TH, Chen E, Li L, Saha P, Lee HJ, Huang LS, et al. The constitutive lipid droplet protein PLIN2 regulates autophagy in liver. Autophagy. 2017;13:1130–44. 10.1080/15548627.2017.1319544

[8]

Straub BK, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P. Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology. 2008;47:1936–46. 10.1002/hep.22268

[9]

Kaushik S, Cuervo AM. AMPK-dependent phosphorylation of lipid droplet protein PLIN2 triggers its degradation by CMA. Autophagy. 2016;12:432–8. 10.1080/15548627.2015.1124226

[10]

Lombard DB, Alt FW, Cheng HL, Bunkenborg J, Streeper RS, Mostoslavsky R, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007;27:8807–14. 10.1128/mcb.01636-07

[11]

Jin L, Galonek H, Israelian K, Choy W, Morrison M, Xia Y, et al. Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3. Protein Sci. 2009;18:514–25. 10.1002/pro.50

[12]

Yang Y, Hubbard BP, Sinclair DA, Tong Q. Characterization of murine SIRT3 transcript variants and corresponding protein products. J Cell Biochem. 2010;111:1051–8. 10.1002/jcb.22795

[13]

Yang Y, Chen KY, Tong Q. Murine Sirt3 protein isoforms have variable half-lives. Gene. 2011;488:46–51. 10.1016/j.gene.2011.07.029

[14]

Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B, Lombard DB, et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature. 2010;464:121–5. 10.1038/nature08778

[15]

Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, et al. Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J. 2011;433:505–14. 10.1042/bj20100791

[16]

Tong W, Ju L, Qiu M, Xie Q, Chen Y, Shen W, et al. Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway. Hepatol Res. 2016;46:933–43. 10.1111/hepr.12634

[17]

Kim HJ, Joe Y, Yu JK, Chen YQ, Jeong SO, Mani N, et al. Carbon monoxide protects against hepatic ischemia/reperfusion injury by modulating the miR-34a/SIRT1 pathway. Biochim Biophys Acta. 2015;1852:1550–9. 10.1016/j.bbadis.2015.04.017

[18]

Yang Y, Cimen H, Han MJ, Shi T, Deng JH, Koc H, et al. NAD+−dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. J Biol Chem. 2010;285:7417–29. 10.1074/jbc.m109.053421

[19]

Lin LG, Pan WJ, Chen KY, Wang F, Gengler J, Sun YX, et al. Adipocyte expression of PU.1 transcription factor causes insulin resistance through upregulation of inflammatory cytokine gene expression and ROS production. Am J Physiol Endocrinol Metab. 2012;302:E1550–9. 10.1152/ajpendo.00462.2011

[20]

Liu JX, Shen SN, Tong Q, Wang YT, Lin LG. Honokiol protects hepatocytes from oxidative injury through mitochondrial deacetylase SIRT3. Eur J Pharm. 2018;834:176–87. 10.1016/j.ejphar.2018.07.036

[21]

Shen S, Liao Q, Feng Y, Liu J, Pan R, Lee SM, et al. Myricanol mitigates lipid accumulation in 3T3-L1 adipocytes and high fat diet-fed zebrafish via activating AMP-activated protein kinase. Food Chem. 2019;270:305–14. 10.1016/j.foodchem.2018.07.117

[22]

Li D, Liu Q, Sun W, Chen X, Wang Y, Sun Y, et al. 1,3,6,7-Tetrahydroxy-8-prenylxanthone ameliorates inflammatory responses resulting from the paracrine interaction of adipocytes and macrophages. Br J Pharm. 2018;175:1590–606. 10.1111/bph.14162

[23]

Lin L, Lee JH, Bongmba OY, Ma X, Zhu X, Sheikh-Hamad D, et al. The suppression of ghrelin signaling mitigates age-associated thermogenic impairment. Aging. 2014;6:1019–32. 10.18632/aging.100706

[24]

Shen S, Liao Q, Liu J, Pan R, Lee SM, Lin L. Myricanol rescues dexamethasone-induced muscle dysfunction via a sirtuin 1-dependent mechanism. J Cachex- Sarcopenia Muscle. 2019;10:429–44. 10.1002/jcsm.12393

[25]

Martinez-Lopez N, Singh R. Autophagy and Lipid Droplets in the Liver. Annu Rev Nutr. 2015;35:215–37. 10.1146/annurev-nutr-071813-105336

[26]

Bao J, Scott I, Lu Z, Pang L, Dimond CC, Gius D, et al. SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity. Free Radic Biol Med. 2010;49:1230–7. 10.1016/j.freeradbiomed.2010.07.009

[27]

Hirschey MD, Shimazu T, Jing E, Grueter CA, Collins AM, Aouizerat B, et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome. Mol Cell. 2011;44:177–90. 10.1016/j.molcel.2011.07.019

[28]

Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65–75. 10.1016/j.cell.2014.02.049

[29]

Ricchi M, Odoardi MR, Carulli L, Anzivino C, Ballestri S, Pinetti A, et al. Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol. 2009;24:830–40. 10.1111/j.1440-1746.2008.05733.x

[30]

Moravcova A, Cervinkova Z, Kucera O, Mezera V, Rychtrmoc D, Lotkova H. The effect of oleic and palmitic acid on induction of steatosis and cytotoxicity on rat hepatocytes in primary culture. Physiol Res. 2015;64:S627–36. 10.33549/physiolres.933224

[31]

Dissection of the Autophagosome Maturation Process by a Novel Reporter Protein, Tandem Fluorescent-Tagged LC3

Shunsuke Kimura, Takeshi Noda, Tamotsu Yoshimori

Autophagy 2007 10.4161/auto.4451

[32]

Alers S, Loffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol. 2012;32:2–11. 10.1128/mcb.06159-11

[33]

Garcia D, Shaw RJ. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell. 2017;66:789–800. 10.1016/j.molcel.2017.05.032

[34]

Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy

Daniel F. Egan, David B. Shackelford, Maria M. Mihaylova et al.

Science 2011 10.1126/science.1196371

[35]

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

Joungmok Kim, Mondira Kundu, Benoit Viollet et al.

Nature Cell Biology 2011 10.1038/ncb2152

[36]

Miyazaki M, Kim YC, Ntambi JM. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J Lipid Res. 2001;42:1018–24. 10.1016/s0022-2275(20)31589-3

[37]

Attie AD, Krauss RM, Gray-Keller MP, Brownlie A, Miyazaki M, Kastelein JJ, et al. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res. 2002;43:1899–907. 10.1194/jlr.m200189-jlr200

[38]

Hulver MW, Berggren JR, Carper MJ, Miyazaki M, Ntambi JM, Hoffman EP, et al. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab. 2005;2:251–61. 10.1016/j.cmet.2005.09.002

[39]

AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

Albert Herms, Marta Bosch, Babu J.N. Reddy et al.

Nature Communications 2015 10.1038/ncomms8176

[40]

Ranhotra HS. Up-regulation of orphan nuclear estrogen-related receptor alpha expression during long-term caloric restriction in mice. Mol Ccell Biochem. 2009;332:59–65. 10.1007/s11010-009-0174-6

[41]

Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci USA. 2006;103:10224–9. 10.1073/pnas.0603968103

[42]

Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest. 2009;119:2758–71.

[43]

Ansari A, Rahman MS, Saha SK, Saikot FK, Deep A, Kim KH. Function of the SIRT3 mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerative disease. Aging Cell. 2017;16:4–16. 10.1111/acel.12538

[44]

Shi T, Wang F, Stieren E. Tong Q. SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. J Biol Chem. 2005;280:13560–7. 10.1074/jbc.m414670200

[45]

Koga H, Kaushik S, Cuervo AM. Altered lipid content inhibits autophagic vesicular fusion. FASEB J. 2010;24:3052–65. 10.1096/fj.09-144519

[46]

Mei S, Ni HM, Manley S, Bockus A, Kassel KM, Luyendyk JP, et al. Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes. J Pharm Exp Ther. 2011;339:487–98. 10.1124/jpet.111.184341

[47]

Liang Q, Benavides GA, Vassilopoulos A, Gius D, Darley-Usmar V, Zhang J. Bioenergetic and autophagic control by Sirt3 in response to nutrient deprivation in mouse embryonic fibroblasts. Biochem J. 2013;454:249–57. 10.1042/bj20130414

[48]

Shi L, Zhang T, Zhou Y, Zeng X, Ran L, Zhang Q, et al. Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1alpha-Sirt3 signaling pathway. Endocrine. 2015;50:378–89. 10.1007/s12020-015-0599-5

[49]

Duan WJ, Li YF, Liu FL, Deng J, Wu YP, Yuan WL, et al. A SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages. Free Radic Biol Med. 2016;95:230–42. 10.1016/j.freeradbiomed.2016.03.022

[50]

Dai SH, Chen T, Li X, Yue KY, Luo P, Yang LK, et al. Sirt3 confers protection against neuronal ischemia by inducing autophagy: Involvement of the AMPK-mTOR pathway. Free Radic Biol Med. 2017;108:345–53. 10.1016/j.freeradbiomed.2017.04.005

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Published: Jun 03, 2019
Vol/Issue: 27(1)
Pages: 329-344
License: View

Authors

T

Tian Zhang

Computer Sciences Dept., Univ. of Wisconsin-Madison

Funding

National Natural Science Foundation of China Award: 81872754

Fundo para o Desenvolvimento das Ciências e da Tecnologia Award: 0031/2019/A1

Cite This Article

Tian Zhang, Jingxin Liu, Shengnan Shen, et al. (2019). SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity. Cell Death & Differentiation, 27(1), 329-344. https://doi.org/10.1038/s41418-019-0356-z

SIRT3 promotes lipophagy and chaperon-mediated autophagy to protect hepatocytes against lipotoxicity

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