Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity

Timothy D. Heden, Jordan M. Johnson, Patrick J. Ferrara, Hiroaki Eshima, Anthony R.P. Verkerke, Edward J. Wentzler, Piyarat Siripoksup, Tara M. Narowski, Chanel B. Coleman, Chien Te Lin, Terence E. Ryan, Paul T. Reidy, Lisandra E. de Castro Brás, Courtney M. Karner, Charles F. Burant, J. Alan Maschek, James E. Cox, Douglas G. Mashek, Gabrielle Kardon, Sihem BoudinaTonya N. Zeczycki, Jared Rutter, Saame Raza Shaikh, Jean E. Vance, Micah J. Drummond, P. Darrell Neufer, Katsuhiko Funai

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


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.

Original languageEnglish (US)
Article numbereaax8352
JournalScience Advances
Issue number9
StatePublished - Sep 11 2019
Externally publishedYes

ASJC Scopus subject areas

  • General


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