Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity.

Published online

Journal Article

Exercise capacity is a strong predictor of all-cause mortality. Skeletal muscle mitochondrial respiratory capacity, its biggest contributor, adapts robustly to changes in energy demands induced by contractile activity. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are regulated. Here, we show that exercise training or muscle disuse alters mitochondrial membrane phospholipids including phosphatidylethanolamine (PE). Addition of PE promoted, whereas removal of PE diminished, mitochondrial respiratory capacity. Unexpectedly, skeletal muscle-specific inhibition of mitochondria-autonomous synthesis of PE caused respiratory failure because of metabolic insults in the diaphragm muscle. While mitochondrial PE deficiency coincided with increased oxidative stress, neutralization of the latter did not rescue lethality. These findings highlight the previously underappreciated role of mitochondrial membrane phospholipids in dynamically controlling skeletal muscle energetics and function.

Full Text

Duke Authors

Cited Authors

  • Heden, TD; Johnson, JM; Ferrara, PJ; Eshima, H; Verkerke, ARP; Wentzler, EJ; Siripoksup, P; Narowski, TM; Coleman, CB; Lin, C-T; Ryan, TE; Reidy, PT; de Castro Brás, LE; Karner, CM; Burant, CF; Maschek, JA; Cox, JE; Mashek, DG; Kardon, G; Boudina, S; Zeczycki, TN; Rutter, J; Shaikh, SR; Vance, JE; Drummond, MJ; Neufer, PD; Funai, K

Published Date

  • September 2019

Published In

Volume / Issue

  • 5 / 9

Start / End Page

  • eaax8352 -

PubMed ID

  • 31535029

Pubmed Central ID

  • 31535029

Electronic International Standard Serial Number (EISSN)

  • 2375-2548

Digital Object Identifier (DOI)

  • 10.1126/sciadv.aax8352


  • eng

Conference Location

  • United States