{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:42:38Z","timestamp":1791412958280,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chemotherapy is extensively used to treat breast cancer and is associated with skeletal muscle deconditioning, which is known to reduce patients' quality of life, treatment efficiency, and overall survival. To date, skeletal muscle mitochondrial alterations represent a major aspect explored in breast cancer patients; nevertheless, the cellular mechanisms remain relatively unknown. This study was dedicated to investigating overall skeletal muscle mitochondrial homeostasis in early breast cancer patients undergoing chemotherapy, including mitochondrial quantity, function, and dynamics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Women undergoing (neo)adjuvant anthracycline\u2010cyclophosphamide and taxane\u2010based chemotherapy participated in this study (56\u00a0\u00b1\u00a012\u00a0years). Two muscle biopsies were collected from the vastus lateralis muscle before the first and after the last chemotherapy administration. Mitochondrial respiratory capacity, reactive oxygen species production, and western blotting analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 11 patients, we found a decrease in key markers of mitochondrial quantity, reaching \u221252.0% for citrate synthase protein levels (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.02) and \u221238.2% for VDAC protein levels (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.04). This mitochondrial content loss is likely explained by reduced mitochondrial biogenesis, as evidenced by a decrease in PGC\u20101\u03b11 protein levels (\u221229.5%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04). Mitochondrial dynamics were altered, as documented by a decrease in MFN2 protein expression (\u221233.4%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01), a key marker of mitochondrial outer membrane fusion. Mitochondrial fission is a prerequisite for mitophagy activation, and no variation was found in either key markers of mitochondrial fission (Fis1 and DRP1) or mitophagy (Parkin, PINK1, and Mul1). Two contradictory hypotheses arise from these results: defective mitophagy, which probably increases the number of damaged and fragmented mitochondria, or a relative increase in mitophagy through elevated mitophagic potential (Parkin\/VDAC ratio; +176.4%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.02). Despite no change in mitochondrial respiratory capacity and COX IV protein levels, we found an elevation in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05 for all substrate additions) without change in antioxidant enzymes. We investigated the apoptosis pathway and found an increase in the protein expression of the apoptosis initiation marker Bax (+72.0%; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04), without variation in the anti\u2010apoptotic protein Bcl\u20102.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrated major mitochondrial alterations subsequent to chemotherapy in early breast cancer patients: (i) a striking reduction in mitochondrial biogenesis, (ii) altered mitochondrial dynamics and potential mitophagy defects, (iii) exacerbated H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production, and (iv) increased initiation of apoptosis. All of these alterations likely explain, at least in part, the high prevalence of skeletal muscle and cardiorespiratory deconditioning classically observed in breast cancer patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12991","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T07:53:47Z","timestamp":1649058827000},"page":"1896-1907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Chemotherapy impairs skeletal muscle mitochondrial homeostasis in early breast cancer patients"],"prefix":"10.1002","volume":"13","author":[{"given":"Joris","family":"Mallard","sequence":"first","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine, ma\u00efeutique et sciences de la sant\u00e9, \u201cMitochondrie, Stress oxydant, Protection musculaire\u201d Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"Facult\u00e9 des Sciences du Sport, Centre Europ\u00e9en d'Enseignement de Recherche et d'Innovation en Physiologie de l'Exercice (CEERIPE) Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyse","family":"Hucteau","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine, ma\u00efeutique et sciences de la sant\u00e9, \u201cMitochondrie, Stress oxydant, Protection musculaire\u201d Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"Facult\u00e9 des Sciences du Sport, Centre Europ\u00e9en d'Enseignement de Recherche et d'Innovation en Physiologie de l'Exercice (CEERIPE) Universit\u00e9 de Strasbourg  Strasbourg France"},{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Laure","family":"Charles","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de m\u00e9decine, ma\u00efeutique et sciences de la sant\u00e9, \u201cMitochondrie, Stress oxydant, Protection musculaire\u201d Universit\u00e9 de Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bender","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Baeza","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"P\u00e9lissie","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe (ICANS)  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Trensz","sequence":"additional","affiliation":[{"name":"Institut de Canc\u00e9rologie Strasbourg Europe 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