Functional mitochondrial heterogeneity in heteroplasmic cells carrying the mitochondrial DNA mutation associated with the MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes)

Pediatr Res. 2000 Aug;48(2):143-50. doi: 10.1203/00006450-200008000-00005.


Most mitochondrial DNA (mtDNA) alterations associated with human disorders are heteroplasmic, i.e. mutant mtDNA molecules coexist with normal ones within the cell. We addressed the possibility of intermitochondrial exchanges through histologic analyses of cybrid clones with increasing proportion of the MELAS (A3243G) mtDNA transfer RNA point mutation. MtDNA-dependent cytochrome c oxidase activity and protein composition as well as mitochondrial membrane potential appeared heterogeneous in individual cells from clonal heteroplasmic cell populations on the basis of confocal and electron microscopy. The number of defective cells increased with increasing mutation load. We conclude that in the presence of a heteroplasmic mtDNA mutation in the cell type that we studied, intermitochondrial molecular exchanges cannot provide an efficient even distribution of the complementing molecules such as wild-type mtDNA, transfer RNA, or protein. Mitochondria in these heteroplasmic cells cannot, therefore, be considered a single functional unit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Fusion
  • Cells, Cultured
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism
  • Humans
  • Hybrid Cells
  • Intracellular Membranes / physiology
  • MELAS Syndrome / genetics*
  • Membrane Potentials
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Muscle, Skeletal / pathology
  • Osteosarcoma
  • Point Mutation*
  • RNA, Transfer, Leu / genetics*
  • Succinate Dehydrogenase / metabolism
  • Tumor Cells, Cultured


  • DNA, Mitochondrial
  • RNA, Transfer, Leu
  • Succinate Dehydrogenase
  • Electron Transport Complex IV