{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:02:36Z","timestamp":1790416956770,"version":"4.1.0"},"reference-count":51,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>Chronic hypoxia reduces aerobic capacity (mitochondrial content) in limb skeletal muscles, and one of the causes seems to be decreased physical activity. Diaphragm and other respiratory muscles, however, may have a different pattern of adaptation as hypoxia increases the work of breathing. Thus, we hypothesized that chronic hypoxia would not reduce mitochondrial content in mouse diaphragm. Adult male C57BL\/6J mice were kept in normoxia (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>= 21%, control) or normobaric hypoxia (Fi<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>= 10%, hypoxia) for 1, 2, and 4 wk. Mice were then killed, and the diaphragm and gastrocnemius muscles collected for analysis. In the diaphragm, cytochrome c oxidase histochemistry showed less intense staining in the hypoxia group. The total content of subunits from the electron transport chain, pyruvate dehydrogenase kinase 1 (PDK1), and voltage-dependent anion channel 1 (VDAC1) was evaluated by Western blot. These proteins decreased by 25\u201330% after 4 wk of hypoxia ( P &lt; 0.05 vs. control for all comparisons), matching a comparable decrease in diaphragmatic mitochondrial volume density (control 33.6 \u00b1 5.5% vs. hypoxia 26.8 \u00b1 6.7%, P = 0.013). Mitochondrial volume density or protein content did not change in gastrocnemius after hypoxia. Hypoxia decreased the content of peroxisome proliferator-activated receptor gamma (PPAR\u03b3) and PPAR\u03b3 cofactor 1-alpha (PGC-1\u03b1) in diaphragm but not in gastrocnemius. PGC-1\u03b1 mRNA levels in diaphragm were also reduced with hypoxia. BCL2\/adenovirus E1B interacting protein 3 (BNIP-3) mRNA levels were upregulated after 1 and 2 wk of hypoxia in diaphragm and gastrocnemius, respectively; BNIP-3 protein content increased only in the diaphragm after 4 wk of hypoxia. Contrary to our hypothesis, these results show that chronic hypoxia decreases mitochondrial content in mouse diaphragm, despite the increase in workload. A combination of reduced mitochondrial biogenesis and increased mitophagy seems to be responsible for the decrease in mitochondrial content in the mouse diaphragm after hypoxia.<\/jats:p>","DOI":"10.1152\/ajpregu.00320.2009","type":"journal-article","created":{"date-parts":[[2009,12,10]],"date-time":"2009-12-10T03:12:14Z","timestamp":1260414734000},"page":"R575-R583","source":"Crossref","is-referenced-by-count":57,"title":["Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia"],"prefix":"10.1152","volume":"298","author":[{"given":"Jorge L.","family":"Gamboa","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco H.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.49.030187.002341"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-122978"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00166-09"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.71.6.2114"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2008.1010"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)01630-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11692-P"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.12.1975"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1957.10.1.81"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-34817-9_16"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1021\/pr060614o"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.1.H241"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2008.1104"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.66.5.2454"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5654-07.2008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401936"},{"key":"B17","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1210\/en.2006-0070","volume":"147","author":"Hondares E","year":"2006","journal-title":"Endocrinology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1024846"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(81)90078-5"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-1024847"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00187-2"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.70.5.1938"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10268"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/BF02189472"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030101"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.14.6225-6234.2005"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfl766"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1152\/advan.00052.2006"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1991.tb09176.x"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1139\/y82-016"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4237"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601689"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2239"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1089\/15270290152608598"},{"key":"B35","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/S0021-9258(18)62305-1","volume":"246","author":"Menzies RA","year":"1971","journal-title":"J Biol Chem"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1991.71.4.1135"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00004.2008"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1984.64.1.1"},{"key":"B39","unstructured":"Niermeyer S , Zamudio S , Moore The People LG.High Altitude: An Exploration of Human Adaptation, edited by , Hornbein TF , Schoene RB. 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