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[초청강연] Dynamic regulation of mitochondrial metabolism in metabolic disease

2022-01-07l Hit 329

Date: 2022-01-10 11:00 ~ 13:00
Speaker: Haejin Yoon (Harvard Medical School)
Professor: 생명과학부
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.