{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:13:22Z","timestamp":1792458802301,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Barth syndrome (BTHS) is a rare X\u2010linked mitochondrial disorder caused by mutations in the\n                      <jats:italic>TAFAZZIN<\/jats:italic>\n                      gene, which disrupts cardiolipin (CL) remodelling and mitochondrial function. While cardiac manifestations of BTHS are well characterized in male patients, the mechanisms underlying skeletal muscle weakness and fatigability are poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated neuromuscular and mitochondrial alterations in a novel murine model (\n                      <jats:italic>Taz<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>PM<\/jats:italic>\n                      <\/jats:sup>\n                      ) carrying a patient\u2010derived D75H point mutation knocked into the\n                      <jats:italic>Tafazzin locus<\/jats:italic>\n                      . This mutation preserves protein abundance but abolishes enzymatic activity. Skeletal muscle function was assessed via weightlifting and hanging tests. Muscle fibre composition and neuromuscular junction (NMJ) integrity were evaluated using immunofluorescence, western blotting and in\u00a0vivo electrophysiology. Mitochondrial morphology was examined by transmission electron microscopy, and bioenergetics were quantified using ultra\u2010performance liquid chromatography. Stress signalling was assessed by western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Male\n                      <jats:italic>Taz<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>PM<\/jats:italic>\n                      <\/jats:sup>\n                      mice exhibited seven\u2010fold elevated total monolysocardiolipin and five\u2010fold reduced mature CL levels, confirming deficient transacylase activity. These mice exhibited lower muscle strength and endurance, 32% smaller muscle fibres of all types and a shift towards fast\u2010twitch type 2B fibres, which are more susceptible to fatigue. Electrophysiological analysis revealed a 60% reduction in motor unit number and an increase in average single motor unit potential, indicating motor neuron remodelling. NMJ protein analysis showed decreased MUSK and DOK7 and increased CHRNA1, suggesting impaired NMJ integrity. Despite mitochondrial structural abnormalities and reduced expression of key mitochondrial proteins (NDUFB8, MCU, TMEM65), resting ATP, phosphocreatine and adenine nucleotide ratios were unchanged in both glycolytic and oxidative muscles. However, stress signalling pathways were markedly activated, including phosphorylation of eIF2\u03b1, increased CHOP, DELE1, p53 expression and altered Wnt\/\u03b2\u2010catenin signalling components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Whole\u2010body deficiency of tafazzin enzymatic activity, as occurs in BTHS, is sufficient to result in widespread neuromuscular remodelling, including fibre size\/type shifts, motor unit loss, NMJ dysregulation and stress pathway activation, without overt energetic failure at rest. These findings suggest that myopathy in BTHS arises not solely from mitochondrial ATP insufficiency but rather from cumulative structural and signalling adaptations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70246","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:32:51Z","timestamp":1773765171000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deficient Cardiolipin Remodelling Alters Muscle Fibre Composition and Neuromuscular Connectivity in Barth Syndrome"],"prefix":"10.1002","volume":"17","author":[{"given":"Catalina","family":"Matias","sequence":"first","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige\u00a0L.","family":"Snider","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth\u00a0A.","family":"Sierra\u00a0Potchanant","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua\u00a0R.","family":"Huot","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Raghav","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute Tufts Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael\u00a0T.","family":"Chin","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute Tufts Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon\u00a0J.","family":"Conway","sequence":"additional","affiliation":[{"name":"Herman B. Wells Center for Pediatric Research Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3503-0528","authenticated-orcid":false,"given":"Jeffrey\u00a0J.","family":"Brault","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Anatomy, Cell Biology &amp; Physiology Indiana University School of Medicine  Indianapolis Indiana 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