The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore

Jason E. Kokoszka, Katrina G. Waymire, Shawn E. Levy, James E. Sligh, Jiyang Cai, Dean P. Jones, Grant R. MacGregor, Douglas C. Wallace

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-465
Number of pages5
JournalNature
Volume427
Issue number6973
DOIs
StatePublished - Jan 29 2004
Externally publishedYes

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Adenosine Diphosphate
Adenosine Triphosphate
Permeability
Cell Death
Proto-Oncogene Proteins c-bcl-2
Hepatocytes
Mitochondria
Voltage-Dependent Anion Channels
Adenine Nucleotides
mitochondrial permeability transition pore
Mitochondrial Membranes
Cytochromes c
Protein Isoforms
Apoptosis
Ligands
Liver
Proteins

ASJC Scopus subject areas

  • General

Cite this

Kokoszka, J. E., Waymire, K. G., Levy, S. E., Sligh, J. E., Cai, J., Jones, D. P., ... Wallace, D. C. (2004). The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 427(6973), 461-465. https://doi.org/10.1038/nature02229

The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. / Kokoszka, Jason E.; Waymire, Katrina G.; Levy, Shawn E.; Sligh, James E.; Cai, Jiyang; Jones, Dean P.; MacGregor, Grant R.; Wallace, Douglas C.

In: Nature, Vol. 427, No. 6973, 29.01.2004, p. 461-465.

Research output: Contribution to journalArticle

Kokoszka, JE, Waymire, KG, Levy, SE, Sligh, JE, Cai, J, Jones, DP, MacGregor, GR & Wallace, DC 2004, 'The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore', Nature, vol. 427, no. 6973, pp. 461-465. https://doi.org/10.1038/nature02229
Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP et al. The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature. 2004 Jan 29;427(6973):461-465. https://doi.org/10.1038/nature02229
Kokoszka, Jason E. ; Waymire, Katrina G. ; Levy, Shawn E. ; Sligh, James E. ; Cai, Jiyang ; Jones, Dean P. ; MacGregor, Grant R. ; Wallace, Douglas C. / The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. In: Nature. 2004 ; Vol. 427, No. 6973. pp. 461-465.
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