Regulation of mitophagy by Sab during adipogenesis

Abstract

Obesity is a global epidemic. Adipogenesis, the synthesis of fat, is elevated in obese individuals. During adipogenesis, mitochondrial density is reduced by a form of self-digestion called mitophagy. Mitophagy is essential to adipogenesis; however, the molecular mechanisms regulating mitophagy are unknown. Existing data suggests that signaling complexes on the outer mitochondrial membrane, such as Sab, facilitate mitophagy. In the present project, the role of post-translational modifications on Sab, in mitochondrial turnover during adipogenesis was investigated. Based on preliminary results we hypothesize that acetylation of Sab on lysine 6 (K6) promotes mitophagy during adipogenesis. Our results showed Sab expression increased in response to elevated levels of fatty acids during adipogenesis and this preceded mitophagy. As a result of nutrient excess, Acetyl Co-A levels increased in mitochondria leading to Sab acetylation and stabilization. Sab-mediated signaling in turn targets mitochondria for degradation. Also, lysine 6 of Sab is necessary for the mitochondrial localization of Sab. The results demonstrate that Sab is required for adipogenesis and represent a novel target for anti-obesity therapeutics.