[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.14348/molcells.2016.2318

Sirt1 and the Mitochondria

Tang, Bor Luen (Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore)

Abstract

Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator- $1{\alpha}$ (PGC- $1{\alpha}$ ) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC- $1{\alpha}$ activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC- $1{\alpha}$ deacetylation and various aspects of cellular physiology and disease.

Keywords

mitochondria; mitochondrial biogenesis; mitophagy; PGC- $1{\alpha}$ ; Sirt1;

Citations & Related Records

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102	Hardie, D.G. (2011). Sensing of energy and nutrients by AMPactivated protein kinase. Am J. Clin. Nutr. 93, 891S-8916. DOI
103	Hathorn, T., Snyder-Keller, A., and Messer, A. (2011). Nicotinamide improves motor deficits and upregulates PGC- $1{\alpha}$ and BDNF gene expression in a mouse model of Huntington's disease. Neurobiol. Dis. 41, 43-50. DOI
104	Herranz, D., Munoz-Martin, M., Canamero, M., Mulero, F., Martinez- Pastor, B., Fernandez-Capetillo, O., and Serrano, M. (2010). Sirt1 improves healthy ageing and protects from metabolic syndrome- associated cancer. Nat. Commun. 1, 3.
105	Higashida, K., Kim, S.H., Jung, S.R., Asaka, M., Holloszy, J.O., and Han, D.H. (2013). Effects of resveratrol and SIRT1 on PGC- $1{\alpha}$ activity and mitochondrial biogenesis: A reevaluation. PLoS Biol. 11, e1001603. DOI
106	Hubbard, B.P., Gomes, A.P., Dai, H., Li, J., Case, A.W., Considine, T., Riera, T.V., Lee, J.E., E, S.Y., Lamming, D.W., et al. (2013). Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339, 1216-1219. DOI
107	Hong, S., Zhao, B., Lombard, D.B., Fingar, D.C., and Inoki, K. (2014). Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation. J. Biol. Chem. 289, 13132- 13141. DOI
108	Hou, X., Xu, S., Maitland-Toolan, K.A., Sato, K., Jiang, B., Ido, Y., Lan, F., Walsh, K., Wierzbicki, M., Verbeuren, T.J., et al. (2008). SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J. Biol. Chem. 283, 20015-20026. DOI
109	Howitz, K.T., Bitterman, K.J., Cohen, H.Y., Lamming, D.W., Lavu, S., Wood, J.G., Zipkin, R.E., Chung, P., Kisielewski, A., Zhang, L.L., et al. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191-196. DOI
110	Jackson, M.D., and Denu, J.M. (2002). Structural identification of 2'- and 3'-O-acetyl-ADP-ribose as novel metabolites derived from the Sir2 family of beta -NAD+-dependent histone/protein deacetylases. J. Biol. Chem. 277, 18535-18544. DOI
111	Jacobs, K.M., Pennington, J.D., Bisht, K.S., Aykin-Burns, N., Kim, H.S., Mishra, M., Sun, L., Nguyen, P., Ahn, B.H., Leclerc, J., et al. (2008). SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression. Int. J. Biol. Sci. 4, 291-299.
112	Jager, S., Handschin, C., St-Pierre, J., and Spiegelman, B.M. (2007). AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc. Natl. Acad. Sci. USA 104, 12017-12022. DOI
113	Kang, H.T., and Hwang, E.S. (2009). Nicotinamide enhances mitochondria quality through autophagy activation in human cells. Aging Cell 8, 426-438. DOI
114	Jang, S.Y., Kang, H.T., and Hwang, E.S. (2012). Nicotinamideinduced mitophagy: event mediated by high NAD+/NADH ratio and SIRT1 protein activation. J. Biol. Chem. 287, 19304-19314. DOI
115	Jin, Q., Yan, T., Ge, X., Sun, C., Shi, X., and Zhai, Q. (2007). Cytoplasm- localized SIRT1 enhances apoptosis. J. Cell. Physiol. 213, 88-97. DOI
116	Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E.A., Caldwell, S.D., Napper, A., Curtis, R., DiStefano, P.S., Fields, S., et al. (2005). Substrate-specific activation of sirtuins by resveratrol. J. Biol. Chem. 280, 17038-17045. DOI
117	Kawai, Y., Garduno, L., Theodore, M., Yang, J., and Arinze, I.J. (2011). Acetylation-deacetylation of the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2) regulates its transcriptional activity and nucleocytoplasmic localization. J. Biol. Chem. 286, 7629-7640. DOI
118	Kim, H., Yang, J., Kim, M.J., Choi, S., Chung, J.R., Kim, J.M., Yoo, Y.H., Chung, J., and Koh, H. (2015). Tumor necrosis factor receptor- associated protein 1 (TRAP1) mutation and TRAP1 inhibitor gamitrinib-triphenylphosphonium (G-TPP) induce a forkhead box O (FOXO)-dependent cell protective signal from mitochondria. J. Biol. Chem. (in press).
119	Koh, H., Kim, H., Kim, M.J., Park, J., Lee, H.J., and Chung, J. (2012). Silent information regulator 2 (Sir2) and Forkhead box O (FOXO) complement mitochondrial dysfunction and dopaminergic neuron loss in Drosophila PTEN-induced kinase 1 (PINK1) null mutant. J. Biol. Chem. 287, 12750-12758. DOI
120	Albani, D., Polito, L., Batelli, S., De Mauro, S., Fracasso, C., Martelli, G., Colombo, L., Manzoni, C., Salmona, M., Caccia, S., et al. (2009). The SIRT1 activator resveratrol protects SK-N-BE cells from oxidative stress and against toxicity caused by alphasynuclein or amyloid-beta (1-42) peptide. J. Neurochem. 110, 1445-1456. DOI
121	Amat, R., Planavila, A., Chen, S.L., Iglesias, R., Giralt, M., and Villarroya, F. (2009). SIRT1 controls the transcription of the peroxisome proliferator-activated receptor-gamma Co-activator- 1alpha (PGC-1alpha) gene in skeletal muscle through the PGC- 1alpha autoregulatory loop and interaction with MyoD. J. Biol. Chem. 284, 21872-21880. DOI
122	Anderson, R.M., Barger, J.L., Edwards, M.G., Braun, K.H., O'Connor, C.E., Prolla, T.A., and Weindruch, R. (2008). Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response. Aging Cell. 7, 101-111. DOI
123	Aquilano, K., Vigilanza, P., Baldelli, S., Pagliei, B., Rotilio, G., and Ciriolo, M.R. (2010). Peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) and sirtuin 1 (SIRT1) reside in mitochondria: possible direct function in mitochondrial biogenesis. J. Biol. Chem. 285, 21590-21599. DOI
124	Dinkova-Kostova, A.T., Baird, L., Holmstrom, K.M., Meyer, C.J., and Abramov, A.Y. (2015). The spatiotemporal regulation of the Keap1-Nrf2 pathway and its importance in cellular bioenergetics. Biochem. Soc. Trans. 43, 602-610. DOI
125	Civitarese, A.E., Carling, S., Heilbronn, L.K., Hulver, M.H., Ukropcova, B., Deutsch, W.A., Smith, S.R., Ravussin, E., and CALERIE Pennington Team (2007). Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med. 4, e76. DOI
126	Cui, L., Jeong, H., Borovecki, F., Parkhurst, C.N., Tanese, N., and Krainc, D. (2006). Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 127, 59-69. DOI
127	Dasgupta, B., and Milbrandt, J. (2007). Resveratrol stimulates AMP kinase activity in neurons. Proc. Natl. Acad. Sci. USA 104, 7217- 7222. DOI
128	Dominy, J.E., Lee, Y., Gerhart-Hines, Z., and Puigserver, P. (2010). Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochim. Biophys. Acta 1804, 1676-1683. DOI
129	Donmez, G., Arun, A., Chung, C.Y., McLean, P.J., Lindquist, S., and Guarente, L. (2012). SIRT1 protects against ${\alpha}$ -synuclein aggregation by activating molecular chaperones. J. Neurosci. 32, 124- 132. DOI
130	Dumont, M., Stack, C., Elipenahli, C., Jainuddin, S., Launay, N., Gerges, M., Starkova, N., Starkov, A.A., Calingasan, N.Y., Tampellini, D., Pujol, A., and Beal, M.F. (2014). PGC- $1{\alpha}$ overexpression exacerbates ${\beta}$ -amyloid and tau deposition in a transgenic mouse model of Alzheimer's disease. FASEB J. 28, 1745-1755. DOI

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3	(2021) Biomolecules Natural Extracts to Augment Energy Expenditure as a Complementary Approach to Tackle Obesity and Associated Metabolic Alterations / 11 (3) , 412
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4	(2021) Metabolites 13C Metabolic Flux Analysis Indicates Endothelial Cells Attenuate Metabolic Perturbations by Modulating TCA Activity / 11 (4) , 226
7	(2016) Stem cells and development SRT1720 Pretreatment Promotes Mitochondrial Biogenesis of Aged Human Mesenchymal Stem Cells and Improves Their Engraftment in Postinfarct Nonhuman Primate Hearts / 30 (7) , 386
8	(2016) Aging Low magnitude vibration alleviates age-related bone loss by inhibiting cell senescence of osteogenic cells in naturally senescent rats / 13 (8) , 12031
3	(2016) Journal of neurochemistry Nicotinamide ameliorates energy deficiency and improves retinal function in Cav‐1<SUP>‐/‐</SUP> mice / 157 (3) , 550
5	(2016) Acta pharmacologica Sinica Pyrroloquinoline quinone promotes mitochondrial biogenesis in rotenone-induced Parkinson’s disease model via AMPK activation / 42 (5) , 665
None	(2016) Ageing research reviews The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: From antioxidant to epigenetic therapy / 67 (None) , 101271
11	(2021) International journal of molecular sciences Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue / 22 (11) , 6025
12	(2021) International journal of molecular sciences Nucleotide Excision Repair: From Molecular Defects to Neurological Abnormalities / 22 (12) , 6220
12	(2021) International journal of molecular sciences Recent Insights into the Interplay of Alpha-Synuclein and Sphingolipid Signaling in Parkinson’s Disease / 22 (12) , 6277
7	(2016) Nature reviews. Rheumatology Linking NAD metabolism and DNA repair to inflammation in SSc / 17 (7) , 381
14	(2016) Journal of cellular and molecular medicine The role of SIRT2 in vascular‐related and heart‐related diseases: A review / 25 (14) , 6470
1	(2016) American journal of physiology. Lung cellular and molecular physiology miR34a: a novel small molecule regulator with a big role in bronchopulmonary dysplasia / 321 (1) , L228
15	(2016) International journal of molecular sciences Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction / 22 (15) , 7772
5	(2016) Journal of receptors and signal transduction MiR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway / 41 (5) , 466
10	(2021) Nutrients Chrysanthemum morifolium Flower Extract Ameliorates Obesity-Induced Inflammation and Increases the Muscle Mitochondria Content and AMPK/SIRT1 Activities in Obese Rats / 13 (10) , 3660
11	(2016) Food science & nutrition The effect of curculigo orchioides (Xianmao) on kidney energy metabolism and the related mechanism in rats based on metabolomics / 9 (11) , 6194
1	(2016) Journal of inflammation Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis / 18 (1) , 31
21	(2016) International journal of molecular sciences MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression / 22 (21) , 11861
22	(2016) International journal of molecular sciences Alzheimer’s Disease and Type 2 Diabetes Mellitus: The Use of MCT Oil and a Ketogenic Diet / 22 (22) , 12310
None	(2021) Molecular therapy. Nucleic acids miR-21 mimic blocks obesity in mice: A novel therapeutic option / 26 (None) , 401
1	(2021) Stem cell research & therapy RETRACTED ARTICLE: MiR-34a inhibitor protects mesenchymal stem cells from hyperglycaemic injury through the activation of the SIRT1/FoxO3a autophagy pathway / 12 (1) , 115
12	(2021) Antioxidants Dietary Phytoestrogens and Their Metabolites as Epigenetic Modulators with Impact on Human Health / 10 (12) , 1893
47	(2021) Journal of agricultural and food chemistry Potential Health Benefits of Whole Grains: Modulation of Mitochondrial Biogenesis and Energy Metabolism / 69 (47) , 14065
6	(2016) Radiation research Protective Effect of Sirt1 against Radiation-Induced Damage / 196 (6) , None
22	(2021) Critical reviews in food science and nutrition Protective role of mitoquinone against impaired mitochondrial homeostasis in metabolic syndrome / 61 (22) , 3857
1	(2022) Reproductive medicine and biology Hypoxia: Role of SIRT1 and the protective effect of resveratrol in ovarian function / 21 (1) , None
None	(2016) Ageing research reviews Deregulated mitochondrial microRNAs in Alzheimer's disease: Focus on synapse and mitochondria / 73 (None) , 101529
None	(2022) Free radical biology & medicine Mitochondrial homeostasis and redox status in cardiovascular diseases: Protective role of the vagal system / 178 (None) , 369
1	(2016) Journal of hepatology : the journal of the European Association for the Study of the Liver Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function / 76 (1) , 11
1	(2022) Antioxidants Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways / 11 (1) , 3
1	(2022) Journal of clinical medicine Bicalutamide Exhibits Potential to Damage Kidney via Destroying Complex I and Affecting Mitochondrial Dynamics / 11 (1) , 135
None	(2022) Cancer letters Exosomes in triple negative breast cancer: From bench to bedside / 527 (None) , 1