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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...

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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
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author 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
author_facet 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
author_sort Heden, Timothy D.
collection PubMed
description 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.
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spelling pubmed-67390962019-09-18 Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity 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 Sci Adv Research Articles 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. American Association for the Advancement of Science 2019-09-11 /pmc/articles/PMC6739096/ /pubmed/31535029 http://dx.doi.org/10.1126/sciadv.aax8352 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
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
Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title_full Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title_fullStr Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title_full_unstemmed Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title_short Mitochondrial PE potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
title_sort mitochondrial pe potentiates respiratory enzymes to amplify skeletal muscle aerobic capacity
topic Research Articles
url 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
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