Gimap3 regulates tissue-specific mitochondrial DNA segregation

PLoS Genet. 2010 Oct 14;6(10):e1001161. doi: 10.1371/journal.pgen.1001161.

Abstract

Mitochondrial DNA (mtDNA) sequence variants segregate in mutation and tissue-specific manners, but the mechanisms remain unknown. The segregation pattern of pathogenic mtDNA mutations is a major determinant of the onset and severity of disease. Using a heteroplasmic mouse model, we demonstrate that Gimap3, an outer mitochondrial membrane GTPase, is a critical regulator of this process in leukocytes. Gimap3 is important for T cell development and survival, suggesting that leukocyte survival may be a key factor in the genetic regulation of mtDNA sequence variants and in modulating human mitochondrial diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • Embryo, Mammalian / cytology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Haplotypes / genetics*
  • Hematopoietic System / metabolism
  • Humans
  • Kidney / metabolism
  • Leukocytes / cytology
  • Leukocytes / metabolism
  • Liver / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Spleen / metabolism

Substances

  • DNA, Mitochondrial
  • Ian4 protein, mouse
  • Membrane Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • GTP-Binding Proteins