{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:13:01Z","timestamp":1790748781921,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AR06991"],"award-info":[{"award-number":["R15AR06991"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008231","name":"Arkansas Biosciences Institute","doi-asserted-by":"publisher","award":["Arkansas Biosciences Institute"],"award-info":[{"award-number":["Arkansas Biosciences Institute"]}],"id":[{"id":"10.13039\/100008231","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Institute for Integrated Healthcare, University of Texas at Tyler","award":["The Institute for Integrated Healthcare, University of Texas at Tyler"],"award-info":[{"award-number":["The Institute for Integrated Healthcare, University of Texas at Tyler"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It is established that cancer cachexia causes limb muscle atrophy and is strongly associated with morbidity and mortality; less is known about how the development of cachexia impacts the diaphragm. The purpose of this study was to investigate cellular signaling mechanisms related to mitochondrial function, reactive oxygen species (ROS) production, and protein synthesis during the development of cancer cachexia. C57BL\/J6 mice developed Lewis Lung Carcinoma for either 0 weeks (Control), 1 week, 2 weeks, 3 weeks, or 4 weeks. At designated time points, diaphragms were harvested and analyzed. Mitochondrial respiratory control ratio was ~50% lower in experimental groups, which was significant by 2 weeks of cancer development, with no difference in mitochondrial content markers COXIV or VDAC. Compared to the controls, ROS was 4-fold elevated in 2-week animals but then was not different at later time points. Only one antioxidant protein, GPX3, was altered by cancer development (~70% lower in experimental groups). Protein synthesis, measured by a fractional synthesis rate, appeared to become progressively lower with the cancer duration, but the mean difference was not significant. The development and progression of cancer cachexia induces marked alterations to mitochondrial function and ROS production in the diaphragm and may contribute to increased cachexia-associated morbidity and mortality.<\/jats:p>","DOI":"10.3390\/ijms21217841","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T20:51:00Z","timestamp":1603399860000},"page":"7841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mitochondrial Function and Protein Turnover in the Diaphragm are Altered in LLC Tumor Model of Cancer Cachexia"],"prefix":"10.3390","volume":"21","author":[{"given":"Megan E.","family":"Rosa-Caldwell","sequence":"first","affiliation":[{"name":"Exercise Science Research Center, Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conner A.","family":"Benson","sequence":"additional","affiliation":[{"name":"Integrative Physiology and Nutrition Laboratory Name, Department of Health and Kinesiology, University of Texas at Tyler, Tyler, TX 75799, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Exercise Science Research Center, Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Exercise Science Research Center, Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyrone A.","family":"Washington","sequence":"additional","affiliation":[{"name":"Exercise Science Research Center, Exercise Muscle Biology Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Greene","sequence":"additional","affiliation":[{"name":"Exercise Science Research Center, Cachexia Research Laboratory, Department of Health, Human Performance and Recreation, University of Arkansas, Fayetteville, AR 72701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5901-7515","authenticated-orcid":false,"given":"Michael P.","family":"Wiggs","sequence":"additional","affiliation":[{"name":"Integrative Physiology and Nutrition Laboratory Name, Department of Health and Kinesiology, University of Texas at Tyler, Tyler, TX 75799, USA"},{"name":"Department of Health, Human Performance and Recreation, Baylor University, Waco, TX 76798, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1001\/jama.2016.20324","article-title":"Trends and Patterns of Disparities in Cancer Mortality Among US Counties, 1980\u20132014","volume":"317","author":"Mokdad","year":"2017","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1001\/jama.2017.7630","article-title":"Colorectal Cancer Mortality Rates in Adults Aged 20 to 54 Years in the United States, 1970\u20132014","volume":"318","author":"Siegel","year":"2017","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1123s","DOI":"10.3945\/ajcn.2010.28608A","article-title":"Skeletal muscle loss: Cachexia, sarcopenia, and inactivity","volume":"91","author":"Evans","year":"2010","journal-title":"Am. 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