{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:37:07Z","timestamp":1776087427215,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK107397"],"award-info":[{"award-number":["DK107397"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM144613"],"award-info":[{"award-number":["GM144613"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK127979"],"award-info":[{"award-number":["DK127979"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG074535"],"award-info":[{"award-number":["AG074535"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The coupling of oxygen consumption to ATP synthesis via oxidative phosphorylation (OXPHOS) is central for cellular energy homeostasis. Some studies suggest exercise training increases the efficiency of ATP synthesis, but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes in mitochondrial lipids might influence OXPHOS efficiency (ATP produced per O\n                      <jats:sub>2<\/jats:sub>\n                      consumed, referred to as P\/O). Peroxisome proliferator\u2010activated receptor gamma coactivator\u20101 alpha (PGC\u20101\u03b1) is a transcriptional co\u2010activator that coordinately regulates exercise\u2010induced adaptations, including mitochondria. We hypothesized that increased PGC\u20101\u03b1 activity might remodel mitochondrial membrane lipids and promote energy efficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice with skeletal muscle\u2010specific overexpression of PGC\u20101\u03b1 (MCK\u2010PGC\u20101\u03b1) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by Western blotting. High\u2010resolution respirometry and fluorometry analyses were performed to characterize mitochondrial bioenergetics (ATP production, O\n                      <jats:sub>2<\/jats:sub>\n                      consumption and P\/O) for permeabilized fibres and isolated mitochondria. Respiratory supercomplexes were assessed by blue native PAGE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK\u2010PGC\u20101\u03b1 mice revealed that PGC\u20101\u03b1 increases the concentrations of cone\u2010shaped lipids such as phosphatidylethanolamine (PE; +25%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), cardiolipin (CL; +184%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and lysophospholipids (+34%\u201394%, all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while decreasing the concentrations of phosphatidylcholine (PC; \u22124%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0020), phosphatidylinositol (PI; \u221217%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and phosphatidic acid (PA; \u221235%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). However, while PGC\u20101\u03b1 overexpression increased the abundance of OXPHOS enzymes (two\u2010 to fourfold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), the rate of O\n                      <jats:sub>2<\/jats:sub>\n                      consumption (1.5\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0030), or the respiratory supercomplexes (~1.5\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), P\/O values were unaffected by PGC\u20101\u03b1 overexpression in permeabilized fibres or isolated mitochondria.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, overexpression of PGC\u20101\u03b1 promotes the biosynthesis of mitochondrial PE and CL, but neither PGC\u20101\u03b1 nor the mitochondrial membrane lipid remodelling induced in MCK\u2010PGC\u20101\u03b1 mice is sufficient to increase the efficiency of mitochondrial ATP synthesis. These findings indicate that PGC\u20101\u03b1\u2010dependent mechanisms or changes in mitochondrial membrane lipids may be insufficient to alter P\/O. While muscles from MCK\u2010PGC\u20101\u03b1 mice are known not to completely phenocopy adaptations with exercise training, our findings also highlight that there is a need to examine whether exercise training indeed improves P\/O in mouse skeletal muscle.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70090","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T06:59:59Z","timestamp":1760079599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Skeletal Muscle PGC\u20101\u03b1 Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis"],"prefix":"10.1002","volume":"16","author":[{"given":"Takuya","family":"Karasawa","sequence":"first","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition &amp; Integrative Physiology University of Utah  Salt Lake City Utah USA"},{"name":"Research Institute for Sport Science Nippon Sport Science University  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran\u00a0Hee","family":"Choi","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition &amp; Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar\u00a0A.","family":"Meza","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition &amp; Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition &amp; Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.\u00a0Alan","family":"Maschek","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Metabolomics Core Research Facility University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda\u00a0S.","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Electron Microscopy Core Facility University of Utah  Salt Lake City Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James\u00a0E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Metabolomics Core Research Facility University of Utah  Salt Lake City Utah 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