{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T22:31:33Z","timestamp":1769812293444,"version":"3.49.0"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T00:00:00Z","timestamp":1346025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["1R01EY018876"],"award-info":[{"award-number":["1R01EY018876"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:p>\n                    Mitochondrial genome (mtDNA) mutation causes highly variable clinical features, and its pathogenesis is not fully understood. In this study, we analyzed the heteroplasmic mtDNA mutation C4936T (p.T156I) in ND2 of complex I and the homoplasmic mtDNA mutation A9181G (p.S219G) in ATPase 6 of complex V. Using cybrid technology, we found that in a high\u2010glucose medium in which cultured cells mainly depend on anaerobic glycolysis for energy, the C4936T mutation inhibited cell growth by 50%. Oxygen consumption and reactive oxygen species production were also reduced by 60 and 75%, respectively. Because the subject also had conjunctiva carcinoma, we further tested whether the C4936T mutation was associated with tumor formation. In an anchorage\u2010dependant growth test, we found that only cells with a high level of C4936T mutation formed colonies. In contrast, when the cells grew in a galactose medium in which cells were forced to generate ATP through oxidative phosphorylation, the C4936T mutation protected cells from apoptosis probably caused by the A9181G mutation. Our results suggest that the phenotype caused by mtDNA mutations may depend on the availability of the nutrients. This gene\u2010environment interaction may contribute to the complexity of pathogenesis and clinical phenotypes caused by mtDNA mutation.\u2014Zhang, C., Huang, V. H., Simon, M., Sharma, L. K., Fan, W., Haas, R., Wallace, D. C., Bai, Y., Huang, T. Heteroplasmic mutations of the mitochondrial genome cause paradoxical effects on mitochondrial functions.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 4914\u20134924 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-206532","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T23:11:32Z","timestamp":1346109092000},"page":"4914-4924","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Heteroplasmic mutations of the mitochondrial genome cause paradoxical effects on mitochondrial functions"],"prefix":"10.1096","volume":"26","author":[{"given":"Chengkang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California\u2013Irvine Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent H.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California\u2013Irvine Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariella","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California\u2013Irvine Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lokendra K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Developmental Biology The Salk Institute for Biological Studies La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California\u2013Irvine Irvine California USA"},{"name":"Department of Neurosciences University of California\u2013San Diego La Jolla California USA"},{"name":"Department of Pediatrics University of California\u2013San Diego La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas C.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Children's Hospital of Philadelphia Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yidong","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cellular and Structural Biology University of Texas Health Science Center San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taosheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California\u2013Irvine Irvine California USA"},{"name":"Department of Pathology University of California\u2013Irvine Irvine California USA"},{"name":"Department of Developmental and Cell Biology University of California\u2013Irvine Irvine California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,27]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Mitochondria","author":"Scheffler I. 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