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Adenine nucleotide translocase family: four isoforms for apoptosis modulation in cancer

Oncogene volume 30, pages 883–895 (2011)Cite this article

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Abstract

Mitochondria have important functions in mammalian cells as the energy powerhouse and integrators of the mitochondrial pathway of apoptosis. The adenine nucleotide translocase (ANT) is a family of proteins involved in cell death pathways that perform distinctly opposite functions to regulate cell fate decisions. On the one hand, ANT catalyzes the adenosine triphosphate export from the mitochondrial matrix to the intermembrane space with the concomitant import of ADP from the intermembrane space to the matrix. On the other hand, during periods of stress, ANT could function as a lethal pore and trigger the process of mitochondrial membrane permeabilization, which leads irreversibly to cell death. In human, ANT is encoded by four homologous genes, whose expression is not only tissue specific, but also varies according to the pathophysiological state of the cell. Recent evidence revealed a differential role of the ANT isoforms in apoptosis and a deregulation of their expression in cancer. In this review, we introduce the current knowledge of ANT in apoptosis and cancer cells and propose a novel classification of ANT isoforms.

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Abbreviations

ANT:

adenine nucleotide translocase

BA:

bongkrekic acid

Ca2+:

calcium

CAT:

carboxyatractyloside

CsA:

cyclosporin A

CypD:

cyclophilin D

ΔΨm:

mitochondrial transmembrane potential

ER:

endoplasmic reticulum

MMP:

mitochondrial membrane permeabilization

IM:

inner membrane

OM:

outer membrane

PiC:

phosphate carrier

PTPC:

permeability transition pore complex

ROS:

reactive oxygen species

UCP1:

uncoupling protein 1

VDAC:

voltage-dependent anion channel

Vpr:

viral protein R

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Acknowledgements

The work of CB and CP are supported by le Centre National de la Recherche Scientifique (CNRS) and l’Agence Nationale de la Recherche (ANR, ANR-08PCVI-0008-01). CB is also supported by l’Institut National pour le Cancer (INCa, 2008-1-PL BIO-04-CNS ON1) and l’Université Paris Sud (Programme Attractivité). CB thanks M Nunez for the help in the preparation of Figure 2 and current and past laboratory members for their invaluable contribution.

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Authors and Affiliations

  1. Univ Paris-Sud, Châtenay-Malabry, France

    C Brenner & C Pertuiset

  2. INSERM UMR-S 769, Châtenay-Malabry, France

    C Brenner & C Pertuiset

  3. PRES UniverSud Paris, Châtenay-Malabry, France

    C Brenner & C Pertuiset

  4. Department of Physiology, Apoptosis, ROS and Cancer Biology Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

    K Subramaniam & S Pervaiz

  5. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore

    S Pervaiz

  6. Duke-NUS Graduate Medical School, Singapore

    S Pervaiz

  7. Singapore-MIT Alliance, Singapore

    S Pervaiz

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  1. C Brenner
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  2. K Subramaniam
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  3. C Pertuiset
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Correspondence to C Brenner.

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Brenner, C., Subramaniam, K., Pertuiset, C. et al. Adenine nucleotide translocase family: four isoforms for apoptosis modulation in cancer. Oncogene 30, 883–895 (2011). https://doi.org/10.1038/onc.2010.501

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  • DOI: https://doi.org/10.1038/onc.2010.501

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