Cargando…

Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity

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 st...

Descripción completa

Detalles Bibliográficos
Autores principales: Heden, Timothy D., Johnson, Jordan M., Ferrara, Patrick J., Eshima, Hiroaki, Verkerke, Anthony R. P., Wentzler, Edward J., Siripoksup, Piyarat, Narowski, Tara M., Coleman, Chanel B., Lin, Chien-Te, Ryan, Terence E., Reidy, Paul T., de Castro Brás, Lisandra E., Karner, Courtney M., Burant, Charles F., Maschek, J. Alan, Cox, James E., Mashek, Douglas G., Kardon, Gabrielle, Boudina, Sihem, Zeczycki, Tonya N., Rutter, Jared, Shaikh, Saame Raza, Vance, Jean E., Drummond, Micah J., Neufer, P. Darrell, Funai, Katsuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739096/
https://www.ncbi.nlm.nih.gov/pubmed/31535029
http://dx.doi.org/10.1126/sciadv.aax8352
Descripción
Sumario: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.