Sirtuin 3

Publication Title: 
Molecular and Cellular Biology

SIRT3 is a member of the Sir2 family of NAD(+)-dependent protein deacetylases that promotes longevity in many organisms. The processed short form of SIRT3 is a well-established mitochondrial protein whose deacetylase activity regulates various metabolic processes. However, the presence of full-length (FL) SIRT3 in the nucleus and its functional importance remain controversial. Our previous studies demonstrated that nuclear FL SIRT3 functions as a histone deacetylase and is transcriptionally repressive when artificially recruited to a reporter gene.

Author(s): 
Iwahara, Toshinori
Bonasio, Roberto
Narendra, Varun
Reinberg, Danny
Publication Title: 
Clinical Science (London, England: 1979)

Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways.

Author(s): 
Kitada, Munehiro
Kume, Shinji
Takeda-Watanabe, Ai
Kanasaki, Keizo
Koya, Daisuke
Publication Title: 
PloS One

SIRT3, a mitochondrial sirtuin belonging to nicotinamide adenine nucleotide (NAD) dependent deacetylases, is implicated in metabolism, longevity and carcinogenesis. SIRT3 expression and its significance in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we demonstrated that SIRT3 expression in HCC tissue was much lower than that in paracarcinoma tissue, at both mRNA and protein levels. The cutoff value for low SIRT3 expression in HCC was defined according to receiver operating characteristic curve (ROC) analysis.

Author(s): 
Zhang, Chris Zhiyi
Liu, Lili
Cai, Muyan
Pan, Yinghua
Fu, Jia
Cao, Yun
Yun, Jingping
Publication Title: 
Cellular and molecular life sciences: CMLS

Reduction of nutrient intake without malnutrition positively influences lifespan and healthspan from yeast to mice and exerts some beneficial effects also in humans. The AMPK-FoxO axis is one of the evolutionarily conserved nutrient-sensing pathways, and the FOXO3A locus is associated with human longevity. Interestingly, FoxO3A has been reported to be also a mitochondrial protein in mammalian cells and tissues. Here we report that glucose restriction triggers FoxO3A accumulation into mitochondria of fibroblasts and skeletal myotubes in an AMPK-dependent manner.

Author(s): 
Peserico, Alessia
Chiacchiera, Fulvio
Grossi, Valentina
Matrone, Antonio
Latorre, Dominga
Simonatto, Marta
Fusella, Aurora
Ryall, James G.
Finley, Lydia W. S.
Haigis, Marcia C.
Villani, Gaetano
Puri, Pier Lorenzo
Sartorelli, Vittorio
Simone, Cristiano
Publication Title: 
Current Opinion in Oncology

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies on mammalian sirtuins that coordinately regulate cellular metabolic homeostasis upon fasting and to summarize the beneficial effects of fasting on carcinogenesis and cancer therapy. RECENT FINDINGS: Recent studies have demonstrated that fasting may protect normal cells and mice from the metabolic conditions that are harmful as well as decrease the incidence of carcinogenesis. Fasting could also slow the tumor growth and augment the efficacy of certain systemic agents/chemotherapy drugs in various cancers.

Author(s): 
Zhu, Yueming
Yan, Yufan
Gius, David R.
Vassilopoulos, Athanassios
Publication Title: 
Clinical Science (London, England: 1979)

Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways.

Author(s): 
Kitada, Munehiro
Kume, Shinji
Takeda-Watanabe, Ai
Kanasaki, Keizo
Koya, Daisuke
Publication Title: 
Current Opinion in Oncology

PURPOSE OF REVIEW: The purpose of this review is to highlight recent studies on mammalian sirtuins that coordinately regulate cellular metabolic homeostasis upon fasting and to summarize the beneficial effects of fasting on carcinogenesis and cancer therapy. RECENT FINDINGS: Recent studies have demonstrated that fasting may protect normal cells and mice from the metabolic conditions that are harmful as well as decrease the incidence of carcinogenesis. Fasting could also slow the tumor growth and augment the efficacy of certain systemic agents/chemotherapy drugs in various cancers.

Author(s): 
Zhu, Yueming
Yan, Yufan
Gius, David R.
Vassilopoulos, Athanassios
Publication Title: 
Diabetes

OBJECTIVE: We determined whether reduced insulin sensitivity, mitochondrial dysfunction, and other age-related dysfunctions are inevitable consequences of aging or secondary to physical inactivity. RESEARCH DESIGN AND METHODS: Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and ATP production in mitochondria isolated from vastus lateralis biopsies of 42 healthy sedentary and endurance-trained young (18-30 years old) and older (59-76 years old) subjects. Expression of proteins involved in fuel metabolism was measured by mass spectrometry.

Author(s): 
Lanza, Ian R.
Short, Daniel K.
Short, Kevin R.
Raghavakaimal, Sreekumar
Basu, Rita
Joyner, Michael J.
McConnell, Joseph P.
Nair, K. Sreekumaran
Publication Title: 
The Journal of Biological Chemistry

SIRT3 is a major mitochondrial NAD(+)-dependent protein deacetylase playing important roles in regulating mitochondrial metabolism and energy production and has been linked to the beneficial effects of exercise and caloric restriction. SIRT3 is emerging as a potential therapeutic target to treat metabolic and neurological diseases.

Author(s): 
Jin, Lei
Wei, Wentao
Jiang, Yaobin
Peng, Hao
Cai, Jianhua
Mao, Chen
Dai, Han
Choy, Wendy
Bemis, Jean E.
Jirousek, Michael R.
Milne, Jill C.
Westphal, Christoph H.
Perni, Robert B.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Sirt3 is a member of the sirtuin family of protein deacetylases that is localized in mitochondria and regulates mitochondrial function. Sirt3 expression in skeletal muscle is decreased in models of type 1 and type 2 diabetes and regulated by feeding, fasting, and caloric restriction. Sirt3 knockout mice exhibit decreased oxygen consumption and develop oxidative stress in skeletal muscle, leading to JNK activation and impaired insulin signaling.

Author(s): 
Jing, Enxuan
Emanuelli, Brice
Hirschey, Matthew D.
Boucher, Jeremie
Lee, Kevin Y.
Lombard, David
Verdin, Eric M.
Kahn, C. Ronald

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