Search tips
Search criteria 


Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. 1991 April; 11(4): 2236–2244.
PMCID: PMC359920

In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria.


A severe mitochondrial protein synthesis defect in myoblasts from a patient with mitochondrial myopathy was transferred with myoblast mitochondria into two genetically unrelated mitochondrial DNA (mtDNA)-less human cell lines, pointing to an mtDNA alteration as being responsible and sufficient for causing the disease. The transfer of the defect correlated with marked deficiencies in respiration and cytochrome c oxidase activity of the transformants and the presence in their mitochondria of mtDNA carrying a tRNA(Lys) mutation. Furthermore, apparently complete segregation of the defective genotype and phenotype was observed in the transformants derived from the heterogeneous proband myoblast population, suggesting that the mtDNA heteroplasmy in this population was to a large extent intercellular. The present work thus establishes a direct link between mtDNA alteration and a biochemical defect.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.1M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. [PubMed]
  • Attardi G, Schatz G. Biogenesis of mitochondria. Annu Rev Cell Biol. 1988;4:289–333. [PubMed]
  • Capaldi RA. Mitochondrial myopathies and respiratory chain proteins. Trends Biochem Sci. 1988 Apr;13(4):144–148. [PubMed]
  • Ching E, Attardi G. High-resolution electrophoretic fractionation and partial characterization of the mitochondrial translation products from HeLa cells. Biochemistry. 1982 Jun 22;21(13):3188–3195. [PubMed]
  • DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC. Mitochondrial myopathies. Ann Neurol. 1985 Jun;17(6):521–538. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Fung CH, Khachadurian AK. Suppression of synthesis and esterification of cholesterol and stimulation of low density lipoprotein receptor activity by polyoxyethylated cholesterol in cultured human fibroblasts. J Biol Chem. 1980 Jan 25;255(2):676–680. [PubMed]
  • Holt IJ, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature. 1988 Feb 25;331(6158):717–719. [PubMed]
  • Holt IJ, Miller DH, Harding AE. Genetic heterogeneity and mitochondrial DNA heteroplasmy in Leber's hereditary optic neuropathy. J Med Genet. 1989 Dec;26(12):739–743. [PMC free article] [PubMed]
  • Holt IJ, Harding AE, Petty RK, Morgan-Hughes JA. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet. 1990 Mar;46(3):428–433. [PubMed]
  • Kim SH, Suddath FL, Quigley GJ, McPherson A, Sussman JL, Wang AH, Seeman NC, Rich A. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA. Science. 1974 Aug 2;185(4149):435–440. [PubMed]
  • Meola G, Scarpini E, Velicogna M, Mottura A, Baron PL, Beretta S, Scarlato G. Analysis of fibronectin expression during human muscle differentiation. Basic Appl Histochem. 1986;30(2):153–163. [PubMed]
  • Mitchell CH, Attardi G. Cytoplasmic transfer of chloramphenicol resistance in a human cell line. Somatic Cell Genet. 1978 Nov;4(6):737–744. [PubMed]
  • Moraes CT, Schon EA, DiMauro S, Miranda AF. Heteroplasmy of mitochondrial genomes in clonal cultures from patients with Kearns-Sayre syndrome. Biochem Biophys Res Commun. 1989 Apr 28;160(2):765–771. [PubMed]
  • Normanly J, Abelson J. tRNA identity. Annu Rev Biochem. 1989;58:1029–1049. [PubMed]
  • Oliver NA, Greenberg BD, Wallace DC. Assignment of a polymorphic polypeptide to the human mitochondrial DNA unidentified reading frame 3 gene by a new peptide mapping strategy. J Biol Chem. 1983 May 10;258(9):5834–5839. [PubMed]
  • Ozawa T, Yoneda M, Tanaka M, Ohno K, Sato W, Suzuki H, Nishikimi M, Yamamoto M, Nonaka I, Horai S. Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1240–1247. [PubMed]
  • Rich A, RajBhandary UL. Transfer RNA: molecular structure, sequence, and properties. Annu Rev Biochem. 1976;45:805–860. [PubMed]
  • Rosing HS, Hopkins LC, Wallace DC, Epstein CM, Weidenheim K. Maternally inherited mitochondrial myopathy and myoclonic epilepsy. Ann Neurol. 1985 Mar;17(3):228–237. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990 Jun 15;61(6):931–937. [PubMed]
  • Storrie B, Attardi G. Expression of the mitochondrial genome in HeLa cells. 13. Effect of selective inhibition of cytoplasmic or mitochondrial protein synthesis on mitochondrial nucleic acid synthesis. J Mol Biol. 1972 Nov 14;71(2):177–199. [PubMed]
  • Vilkki J, Savontaus ML, Nikoskelainen EK. Genetic heterogeneity in Leber hereditary optic neuroretinopathy revealed by mitochondrial DNA polymorphism. Am J Hum Genet. 1989 Aug;45(2):206–211. [PubMed]
  • Wallace DC. Mitotic segregation of mitochondrial DNAs in human cell hybrids and expression of chloramphenicol resistance. Somat Cell Mol Genet. 1986 Jan;12(1):41–49. [PubMed]
  • Wallace DC. Mitochondrial DNA mutations and neuromuscular disease. Trends Genet. 1989 Jan;5(1):9–13. [PubMed]
  • Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ, 2nd, Nikoskelainen EK. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988 Dec 9;242(4884):1427–1430. [PubMed]
  • Wiseman A, Attardi G. Cytoplasmically determined human cell mutants defective in mitochondrial ribosome assembly. Mol Gen Genet. 1982;186(3):364–371. [PubMed]
  • Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology. 1988 Sep;38(9):1339–1346. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)