Affordable Access

deepdyve-link
Publisher Website

PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle.

Authors
  • Yoon, Haejin1
  • Spinelli, Jessica B1
  • Zaganjor, Elma1
  • Wong, Samantha J1
  • German, Natalie J1
  • Randall, Elizabeth C2
  • Dean, Afsah3
  • Clermont, Allen3
  • Paulo, Joao A1
  • Garcia, Daniel4
  • Li, Hao5
  • Rombold, Olivia1
  • Agar, Nathalie Y R6
  • Goodyear, Laurie J3
  • Shaw, Reuben J4
  • Gygi, Steven P1
  • Auwerx, Johan5
  • Haigis, Marcia C7
  • 1 Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
  • 2 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Boston, MA, USA.
  • 3 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Boston, MA, USA.
  • 4 The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA, USA.
  • 5 Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland. , (Switzerland)
  • 6 Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Boston, MA, USA; Departments of Neurosurgery and Cancer Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • 7 Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell metabolism
Publication Date
Aug 04, 2020
Volume
32
Issue
2
Identifiers
DOI: 10.1016/j.cmet.2020.06.017
PMID: 32663458
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2020 Elsevier Inc. All rights reserved.

Report this publication

Statistics

Seen <100 times