Mitochondrial permeability: dual role for the ADP/ATP translocator?
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.
Department of Biochemistry, University of Bristol, Bristol BS8 1TD, UK. a.halestrap@bristol.ac.uk
Andrew P
AP
Halestrap
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D017353:Gene Deletion; D020043:Genes, Essential; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015203:Reproducibility of Results
D000081406:Peptidyl-Prolyl Isomerase F; C000631446:PPIF protein, mouse; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D021983:Cyclophilins; D002118:Calcium