{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:13:33Z","timestamp":1791404013255,"version":"4.3.3"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1991,12]]},"abstract":"<jats:p>Mutant mitochondrial DNA with large-scale deletions (delta-mtDNA) has been frequently observed in patients with chronic progressive external ophthalmoplegia (CPEO), a subgroup of the mitochondrial encephalomyopathies. To exclude involvement of the nuclear genome in expression of the mitochondrial dysfunction characteristic of CPEO, we introduced the mtDNA of a CPEO patient into clonal mtDNA-less HeLa cells and isolated cybrid clones. Quantitation of delta-mtDNA in the cybrids revealed that delta-mtDNA was selectively propagated with higher levels of delta-mtDNA correlating with slower cellular growth rate. In these cybrid clones, translational complementation of the missing tRNAs occurred only when delta-mtDNA was less than 60% of the total mtDNA, whereas accumulation of delta-mtDNA to greater than 60% resulted in progressive inhibition of overall mitochondrial translation as well as reduction of cytochrome c oxidase activity throughout the organelle population. Because these cybrids shared the same nuclear background as HeLa cells, these results suggest that large-scale deletion mutations of mtDNA alone are sufficient for the mitochondrial dysfunction characteristic of CPEO.<\/jats:p>","DOI":"10.1073\/pnas.88.23.10614","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:51:47Z","timestamp":1149061907000},"page":"10614-10618","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":425,"title":["Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction."],"prefix":"10.1073","volume":"88","author":[{"given":"J","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Takemitsu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saitama Cancer Center Research Institute, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1991,12]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.88.23.10614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:19:03Z","timestamp":1649855943000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.88.23.10614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1991,12]]},"references-count":0,"journal-issue":{"issue":"23","published-print":{"date-parts":[[1991,12]]}},"alternative-id":["10.1073\/pnas.88.23.10614"],"URL":"https:\/\/doi.org\/10.1073\/pnas.88.23.10614","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1991,12]]},"assertion":[{"value":"1991-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}