Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy

Makoto Yoneda, Anne Chomyn, Andrea Martinuzzi, Orest Hurko, Giuseppe Attardi

Research output: Contribution to journalArticle

Abstract

The segregation of mutant and wild-type mtDNA was investigated in transformants constructed by transferring human mitochondria from individuals belonging to four pedigrees with the MELAS encephalomyopathy-associated mtDNA mutation (MELAS is mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) into human mtDNA-less (ρo) cells. Five of 13 clonal cell lines containing mixtures of wild-type and mutant mtDNAs were found to undergo a rapid shift of their genotype toward the pure mutant type. The other 8 cell lines, which included 6 exhibiting nearly homoplasmic mutant mtDNA, on the contrary, maintained a stable genotype. Subcloning experiments and growth rate measurements clearly indicated that an intracellular replicative advantage of mutant mtDNA was mainly responsible for the dramatic shift toward the mutant genotype observed in the unstable cell lines.

Original languageEnglish
Pages (from-to)11164-11168
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number23
Publication statusPublished - Dec 1 1992

Keywords

  • Encephalopathy
  • Lactic acidosis
  • Mitochondrial myopathy
  • Stroke-like episodes

ASJC Scopus subject areas

  • Genetics
  • General

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