Emerging role of SIRT3 in mitochondrial dysfunction and cardiovascular diseases

Abstract

As a nicotinamide adenine dinucleotide (NAD)⁺-dependent protein deacetylase, SIRT3 is highly expressed in tissues with high metabolic turnover and mitochondrial content. It has been demonstrated that SIRT3 plays a critical role in maintaining normal mitochondrial biological function through reversible protein lysine deacetylation. SIRT3 has a variety of substrates that are involved in mitochondrial biological processes such as energy metabolism, reactive oxygen species production and clearance, electron transport chain flux, mitochondrial membrane potential maintenance, and mitochondrial dynamics. In the suppression of SIRT3, functional deficiencies of mitochondria contribute to the development of various cardiovascular disorders. Activation of SIRT3 may represent a promising therapeutic strategy for the improvement of mitochondrial function and the treatment of relevant cardiovascular disorders. In the current review, we discuss the emerging roles of SIRT3 in mitochondrial derangements and subsequent cardiovascular malfunctions, including cardiac hypertrophy and heart failure, ischemia-reperfusion injury, and endothelial dysfunction in hypertension and atherosclerosis.

Keywords:

• Cardiovascular diseases
• deacetylation
• mitochondrial dysfunction
• SIRT3

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Natural Science Foundation of Guangdong Province [2016A030313561 and 2017A030313590] and the President Foundation of Nanfang Hospital, Southern Medical University, Guangzhou, China [No. 2015Z001 and No. 2016Z002] for Zhongqing Chen, the National Natural Science Foundation of China [81370226 and 81170297] and the Guangdong Natural Science Foundation Team Project [S2013030013217] for Qiaobing Huang.