The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore.
A sudden increase in permeability of the inner mitochondrial membrane, the so-called mitochondrial permeability transition, is a common feature of apoptosis and is mediated by the mitochondrial permeability transition pore (mtPTP). It is thought that the mtPTP is a protein complex formed by the voltage-dependent anion channel, members of the pro- and anti-apoptotic BAX-BCL2 protein family, cyclophilin D, and the adenine nucleotide (ADP/ATP) translocators (ANTs). The latter exchange mitochondrial ATP for cytosolic ADP and have been implicated in cell death. To investigate the role of the ANTs in the mtPTP, we genetically inactivated the two isoforms of ANT in mouse liver and analysed mtPTP activation in isolated mitochondria and the induction of cell death in hepatocytes. Mitochondria lacking ANT could still be induced to undergo permeability transition, resulting in release of cytochrome c. However, more Ca2+ than usual was required to activate the mtPTP, and the pore could no longer be regulated by ANT ligands. Moreover, hepatocytes without ANT remained competent to respond to various initiators of cell death. Therefore, ANTs are non-essential structural components of the mtPTP, although they do contribute to its regulation.
Pubmed ID: 14749836
- Kokoszka JE
- Waymire KG
- Levy SE
- Sligh JE
- Cai J
- Jones DP
- MacGregor GR
- Wallace DC
January 29, 2004
- Agency: NICHD NIH HHS, Id: R01 HD036437-02
- Agency: NICHD NIH HHS, Id: R01 HD036437-03
- Agency: NICHD NIH HHS, Id: R01 HD036437-04
- Agency: NICHD NIH HHS, Id: R01 HD036437-05
- Agency: NICHD NIH HHS, Id: U01 HD045913-01
- Adenine Nucleotide Translocator 1
- Adenine Nucleotide Translocator 2
- Cell Death
- Gene Deletion
- Ion Channels
- Mice, Knockout
- Mitochondria, Liver
- Mitochondrial Membrane Transport Proteins
- Progressive external ophthalmoplegia with mitochondrial DNA deletions 3 is related to genes SLC25A4, ANT1, T1, PEO3, PEO2, MTDPS12 which are autosomal dominant according to the OMIM database.
- Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type) is related to genes SLC25A4, ANT1, T1, PEO3, PEO2, MTDPS12 which are autosomal recessive according to the OMIM database.