[대학원 생명과학과 세미나 안내]
연사 : 윤혜진 교수(울산과기원)
연제 : Dynamic regulation of mitochondrial metabolism in metabolic disease
일시 : 2022년 05월 06일 (금) 오후 4시 30분
장소 : 대면 및 온라인 화상 강의로 진행됩니다.
초청교수 : 이헌상 교수
Abstract
Metabolism is all chemical reactions involved in maintaining the living state of the cells and the organism. Rapid alterations in cellular metabolism allow tissues to maintain homeostasis during changes in energy availability. The central metabolic regulator acetyl-CoA carboxylase 2 (ACC2) is robustly phosphorylated during cellular energy stress by AMP-activated protein kinase (AMPK) to relieve its suppression of fat oxidation. While ACC2 can also be hydroxylated by prolyl hydroxylase 3 (PHD3), the physiological consequence thereof is poorly understood. We find that ACC2 phosphorylation and hydroxylation occur in an inverse fashion. ACC2 hydroxylation occurs in conditions of high energy and represses fatty acid oxidation. PHD3-null mice demonstrate loss of ACC2 hydroxylation in heart and skeletal muscle and display elevated fatty acid oxidation. Whole body or skeletal muscle-specific PHD3 loss enhances exercise capacity during an endurance exercise challenge. In sum, these data identify an unexpected link between AMPK and PHD3, and a role for PHD3 in acute exercise endurance capacity and skeletal muscle metabolism. Specially, these studies suggest a strategy for metabolic disease for remodeling mitochondrial metabolism through metabolic sensors. These results support a new therapeutic insight of metabolic sensor in physiological and pathological metabolic contexts.
Keywords: Prolyl hydroxylase 3; acetyl-CoA carboxylase 2 modification; exercise capacity; fat catabolism.