Cellular NADâº Level: A Key Determinant of Mitochondrial Quality and Health

Hwang, Eun Seong; Hwang, Sung Yun

Abstract

The quality of mitochondria is a key determinant of mitochondrial ATP production and reactive oxygen species generation; therefore, it plays critical roles in energy homeostasis and cellular health. Mitochondrial quality is governed by mitochondrial turnover, which involves autophagic removal of old mitochondria and biogenesis of new ones. Both activities are critically modulated by sirtuin proteins, in particular, SIRT1 and SIRT3. These proteins activate mitophagy and mitochondrial biogenesis through deacetylation-mediated activation of factors participating in key steps of autophagy and mitochondrial protein expression. They also control other factors involved in maintenance of mitochondrial integrity and in damage prevention. At the same time, the activities and protein levels of SIRT1 and SIRT3 decline during aging, contributing to mitochondrial dysfunction associated with tissue aging and many degenerative diseases. However, recent studies suggest that the activity of the sirtuin proteins can be elevated through modulation of nicotinamide adenine dinucleotide (NAD+) and in physiological settings. An understanding of the underlying molecularpathways is actively sought and practical strategies are proposed based on basic research; nevertheless,their applicability at the clinical and subclinical levels could be better recognized and understood in the field of medicine. To this end, this review discusses the recent understanding of the biochemistry underlying the NADâº-redox mediated modulation of cellular sirtuin activity.