Role of SIRT3 in mitochondrial biology and its therapeutic implications in neurodegenerative disorders

Abstract

Sirtuin 3 (SIRT3), a mitochondrial deacetylase expressed preferentially in high-metabolic-demand tissues including the brain, requires NAD⁺ as a cofactor for catalytic activity. It regulates various processes such as energy homeostasis, redox balance, mitochondrial quality control, mitochondrial unfolded protein response, biogenesis, dynamics and mitophagy by altering protein acetylation status. Reduced SIRT3 expression or activity causes hyperacetylation of hundreds of mitochondrial proteins, which has been linked with neurological abnormalities, neuro-excitotoxicity and neuronal cell death. A body of evidence has suggested, SIRT3 activation as a potential therapeutic modality for age-related brain abnormalities and neurodegenerative disorders.

Keywords: SIRT3; SIRT3 activators; acetylome; aging; deacetylation; exercise; mitochondria; neurodegenerative disorders; neurogenesis; oxidative stress.