SIRT3 is a member of the sirtuin family of protein deacetylases that is preferentially localized to mitochondria. Prominent among the proteins targeted by SIRT3 are enzymes involved in energy metabolism processes, including the respiratory chain, tricarboxylic acid cycle, fatty acid β-oxidation and ketogenesis. Through these actions, SIRT3 controls the flow of mitochondrial oxidative pathways and, consequently, the rate of production of reactive oxygen species. In addition, SIRT3-mediated deacetylation activates enzymes responsible for quenching reactive oxygen species, and thereby exerts a profound protective action against oxidative stress-dependent pathologies, such as cardiac hypertrophy and neural degeneration. SIRT3 also plays a role in multiple additional metabolic processes, from acetate metabolism to brown adipose tissue thermogenesis, often by controlling mitochondrial pathways through the deacetylation of target enzymes. In general, SIRT3 activity and subsequent control of enzymes involved in energy metabolism is consistent with an overall role of protecting against age-related diseases. In fact, experimental and genetic evidence has linked SIRT3 activity with increased lifespan. In the coming years, the identification of drugs and nutrients capable of increasing SIRT3 expression or modulating SIRT3 activity can be expected to provide promising strategies for ameliorating the metabolic syndrome and other oxidative stress-related diseases that appear preferentially with aging, such as cancer, cardiac dysfunction and neural degeneration.
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May 2012
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Review Article|
April 26 2012
SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging
Albert Giralt
;
Albert Giralt
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia and Institut de Biomedicina de la Universitat de Barcelona (IBUB), University of Barcelona, Avda Diagonal 643, Barcelona 08028, Spain, and CIBER Fisitopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Barcelona, Spain
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Francesc Villarroya
Francesc Villarroya
1
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia and Institut de Biomedicina de la Universitat de Barcelona (IBUB), University of Barcelona, Avda Diagonal 643, Barcelona 08028, Spain, and CIBER Fisitopatologia de la Obesidad y Nutrición, Instituto de Salud Carlos III, Barcelona, Spain
1To whom correspondence should be addressed (email fvillarroya@ub.edu).
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Biochem J (2012) 444 (1): 1–10.
Article history
Received:
January 05 2012
Revision Received:
February 29 2012
Accepted:
March 01 2012
Citation
Albert Giralt, Francesc Villarroya; SIRT3, a pivotal actor in mitochondrial functions: metabolism, cell death and aging. Biochem J 15 May 2012; 444 (1): 1–10. doi: https://doi.org/10.1042/BJ20120030
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