Mitochondrial permeability: dual role for the ADP/ATP translocator?

Nature. 2004 Aug 26;430(7003):1 p following 983. doi: 10.1038/nature02816.

Abstract

The ADP/ATP translocator (or adenine nucleotide translocase; ANT) is thought to play a dual role: in the transport of ADP and ATP across the mitochondrial inner membrane and in the formation of the mitochondrial permeability-transition pore (mtPTP), a nonspecific pore that is an important mediator of apoptosis (programmed cell death). However, Kokoszka et al. have shown that mitochondria from livers of 'ANT-knockout' mice, in which the ANT has been genetically inactivated, still possess mtPTP activity. From this, the authors conclude that the ANT is a non-essential component of the mtPTP that may be dispensable for mtPTP-associated cell death. These results, which contradict previous evidence and cast doubt on a widely accepted model for the mtPTP (ref. 1), warrant scrutiny and call for a fundamental reappraisal of the role of the ANT in liver metabolism.

Publication types

  • Comment

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / metabolism
  • Cyclophilins / metabolism
  • Gene Deletion
  • Genes, Essential*
  • Mice
  • Mitochondria, Liver / enzymology
  • Mitochondria, Liver / metabolism*
  • Mitochondrial ADP, ATP Translocases / genetics
  • Mitochondrial ADP, ATP Translocases / metabolism*
  • Models, Biological
  • Peptidyl-Prolyl Isomerase F
  • Reproducibility of Results

Substances

  • Peptidyl-Prolyl Isomerase F
  • PPIF protein, mouse
  • Adenosine Triphosphate
  • Mitochondrial ADP, ATP Translocases
  • Cyclophilins
  • Calcium