{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:42:58Z","timestamp":1792460578297,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL146443"],"award-info":[{"award-number":["R01 HL146443"]}],"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":["S10 OD021758\u201001A1"],"award-info":[{"award-number":["S10 OD021758\u201001A1"]}],"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":["S10 OD030250\u201001A1"],"award-info":[{"award-number":["S10 OD030250\u201001A1"]}],"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":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Doxorubicin (DOX) is a highly effective chemotherapeutic agent whose use can cause respiratory toxicity, increasing patient fatigue and negatively impacting quality of life and survival. These adverse effects occur due to diaphragm muscle mitochondrial accumulation of DOX, where it causes reactive oxygen species production and iron dysregulation. ABCB10 is a mitochondria\u2010localized ATP\u2010binding cassette transporter hypothesized to play a role in the maintenance of mitochondrial redox balance and iron homeostasis, and potentially the mitochondrial export of DOX. This study investigated potential therapeutic effects of ABCB10 to prevent DOX\u2010induced respiratory muscle dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DOX respiratory muscle toxicity was modelled in rats using both single (20\u2009mg\/kg, once) and multicycle (5.7\u2009mg\/kg, 3\u2009cycles) administration. The effects of overexpression and knockdown of ABCB10 on DOX\u2010induced diaphragm dysfunction, mitochondrial DOX accumulation and markers of mitochondrial iron homeostasis were evaluated via administration of rAAV9\u2010MHCK7\u2010ABCB10 or an antisense oligonucleotide targeting ABCB10, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ABCB10 significantly improved diaphragm rate of fatigue (138.2\u2009\u00b1\u200911.66\u2009s vs. 104.6\u2009\u00b1\u20098.79\u2009s in DOX), specific force production (22.12\u2009\u00b1\u20090.70\u2009N\/cm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 18.31\u2009\u00b1\u20091.65\u2009N\/cm\n                      <jats:sup>2<\/jats:sup>\n                      at 160\u2009Hz in DOX) and fibre area (Type I: 1309.05\u2009\u00b1\u200956.86\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 1027.04\u2009\u00b1\u200950.53\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX; Type IIa: 1389.13\u2009\u00b1\u200947.72\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 1027.04\u2009\u00b1\u200950.07\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX; Type IIb\/x: 2590.81\u2009\u00b1\u2009103.21\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 2302.13\u2009\u00b1\u2009138.62\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX) following a single injection of DOX. These improvements did not occur as a result of ABCB10\u2010induced efflux of DOX (1006.03\u2009\u00b1\u2009214.30\u2009pg\/\u03bcg vs. 1008.69\u2009\u00b1\u2009195.62\u2009pg\/\u03bcg in DOX) but were associated with reduced mitochondrial iron (0.17\u2009\u00b1\u20090.02\u2009nmol\/mg vs. 0.23\u2009\u00b1\u20090.02\u2009nmol\/mg in DOX). The beneficial effects on diaphragm rate of fatigue (136.5\u2009\u00b1\u200911.93\u2009s vs. 121.5\u2009\u00b1\u20099.47\u2009s in DOX), specific force production (23.36\u2009\u00b1\u20091.40\u2009N\/cm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 19.26\u2009\u00b1\u20091.21\u2009N\/cm\n                      <jats:sup>2<\/jats:sup>\n                      at 160\u2009Hz in DOX) and fibre area (Type I: 1124.68\u2009\u00b1\u200963.02\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 914.57\u2009\u00b1\u200963.09\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX; Type IIa: 1244.67\u2009\u00b1\u2009106.18\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 950.02\u2009\u00b1\u200962.38\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX; Type IIb\/x: 2548.37\u2009\u00b1\u2009235.69\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      vs. 2222.17\u2009\u00b1\u2009234.61\u2009\u03bcm\n                      <jats:sup>2<\/jats:sup>\n                      in DOX) were also present in rats that received multiple cycles of DOX. Diaphragm rescue with ABCB10 was attendant with reduced mitoferrin 1 gene expression (+1.62\u2009\u00b1\u20090.47 fold vs. +3.85\u2009\u00b1\u20090.99 fold in DOX),\u00a0preservation of mitochondrial function and a reduction in markers of heme synthesis, including Fech (+0.78\u2009\u00b1\u20090.17 fold vs. +0.24\u2009\u00b1\u20090.09 fold in DOX), ALAS1 (+0.54\u2009\u00b1\u20090.18 fold vs. +0.19\u2009\u00b1\u20090.04 fold in DOX), ALAS2 (+0.68\u2009\u00b1\u20090.23 fold vs. +0.33\u2009\u00b1\u20090.11 fold in DOX) and CPOX (+0.84\u2009\u00b1\u20090.16 fold vs. +0.38\u2009\u00b1\u20090.09 fold in DOX). While increasing ABCB10 in the diaphragm prevented DOX respiratory toxicity, reducing its expression did not exacerbate diaphragm dysfunction or mitochondrial DOX and iron accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that ABCB10 can preserve mitochondrial and diaphragm muscle function following DOX treatment by regulating iron redox\u2010cycling and heme synthesis, independent of changes to DOX accumulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70171","type":"journal-article","created":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T00:54:04Z","timestamp":1768611244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mitochondrial Transporter ABCB10 Protects Against Doxorubicin\u2010Induced Respiratory Muscle Dysfunction Independent of Changes to Diaphragm Accumulation"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5437-3097","authenticated-orcid":false,"given":"Ashley\u00a0J.","family":"Smuder","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Doerr","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar\u00a0E.","family":"Jacintho\u00a0Moritz","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branden\u00a0L.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340311799960645"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00161.2019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2018.02.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2016.01.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841860903373716"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304\u20100642IM"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.9014"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477\u20107525\u20107\u2010102"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114818"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21809"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.2.7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.003418"},{"key":"e_1_2_9_14_1","first-page":"219","article-title":"Quantitative Comparison of Toxicity of Anticancer Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man","volume":"50","author":"Freireich E. 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