Heden 2019 Sci Adv

From Bioblast
Jump to: navigation, search
Publications in the MiPMap
Heden TD, Johnson JM, Ferrara PJ, Eshima H, Verkerke ARP, Wentzler EJ, Siripoksup P, Narowski TM, Coleman CB, Lin CT, 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 (2019) Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity. Sci Adv 5:eaax8352.

» PMID: 31535029 Open Access

Heden TD, Johnson JM, Ferrara PJ, Eshima H, Verkerke ARP, Wentzler EJ, Siripoksup P, Narowski TM, Coleman CB, Lin CT, 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 (2019) Sci Adv

Abstract: 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.


Bioblast editor: Plangger M O2k-Network Lab: US NC Greenville Neufer PD, US UT Salt Lake City Funai K


Labels: MiParea: Respiration, mt-Membrane, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Coupling state: LEAK, OXPHOS  Pathway: F, N, S, DQ, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2019-12