{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:14:11Z","timestamp":1791051251541,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,8,30]]},"abstract":"<jats:p>A point mutation in the mtDNA-encoded ATP6 gene (T--&gt;G at nt 8993) associated with Leigh syndrome in two pedigrees was found to decrease ADP-stimulated (state III) respiration and the ratio of ADP molecules phosphorylated to oxygen atoms reduced (ADP\/O ratio) but did not affect 2,4-dinitrophenol (DNP)-uncoupled respiration, suggesting a defective mitochondrial H(+)-translocating ATP synthase. Intact mitochondria isolated from patient and control lymphoblastoid cell lines were tested for state III, ADP-limited (state IV), and DNP-uncoupled respiration with various substrates. Mitochondria isolated from patient lymphoblasts harboring 95-100% of mtDNAs carrying the nt 8993 T--&gt;G mutation showed state III respiration rates 26-50% lower than controls while having normal DNP-uncoupled rates. This resulted in state III\/DNP ratios of 0.52-0.70 in patient mitochondria versus 0.88-0.97 in controls. The ADP\/O ratio was also decreased 30-40% in patient mitochondria. Patient lymphoblasts heteroplasmic for the nt 8993 mutation were enucleated by using Percoll gradients and the cytoplasts were fused to mtDNA-deficient (rho 0) cells by electric shock. Cybrid clones homoplasmic for the wild-type nucleotide (T) at nt 8993 gave state III\/DNP and ADP\/O ratios similar to those of control cybrids, whereas cybrid clones homoplasmic for the mutant nucleotide (G) showed a 24-53% reduction in state III respiration, a state III\/DNP ratio of 0.53-0.64, and a 30% decrease in the ADP\/O ratio. Thus, the reduced state III respiration rates and ADP\/O ratios are linked to the T--&gt;G mutation at nt 8993.<\/jats:p>","DOI":"10.1073\/pnas.91.18.8334","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:53:55Z","timestamp":1149065635000},"page":"8334-8338","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":163,"title":["Cytoplasmic transfer of the mtDNA nt 8993 T--&gt;G (ATP6) point mutation associated with Leigh syndrome into mtDNA-less cells demonstrates cosegregation with a decrease in state III respiration and ADP\/O ratio."],"prefix":"10.1073","volume":"91","author":[{"given":"I","family":"Trounce","sequence":"first","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Neill","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D C","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, GA 30322."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,8,30]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.18.8334","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:55:20Z","timestamp":1649858120000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.18.8334"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,8,30]]},"references-count":0,"journal-issue":{"issue":"18","published-print":{"date-parts":[[1994,8,30]]}},"alternative-id":["10.1073\/pnas.91.18.8334"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.18.8334","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,8,30]]},"assertion":[{"value":"1994-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}