Brief Communications Arising | Published:

Mitochondrial permeability

Dual role for the ADP/ATP translocator?

Naturevolume 430page984 (2004) | Download Citation



Arising from: J. E. Kokoszka et al. Nature 427, 461–464 (2004) 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)1,2,3. However, Kokoszka et al.4 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 death4. These results, which contradict previous evidence1,2 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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Halestrap, A. P. & Brenner, C. Curr. Medicinal Chem. 10, 1507–1525 (2003).

  2. 2

    Halestrap, A. P., Doran, E., Gillespie, J. P. & O'Toole, A. Biochem. Soc. Trans. 28, 170–177 (2000).

  3. 3

    Palmieri, F. Pflugers Arch. 447, 689–709 (2004).

  4. 4

    Kokoszka, J. E. et al. Nature 427, 461–464 (2004).

  5. 5

    Stubbs, M., Vignais, P. V. & Krebs, H. A. Biochem. J. 172, 333–342 (1978).

  6. 6

    Dierks, T., Salentin, A. & Krämer, R. Biochim. Biophys. Acta 1028, 281–288 (1990).

  7. 7

    Brustovetsky, N., Tropschug, M., Heimpel, S., Heidkamper, D. & Klingenberg, M. Biochemistry 41, 11804–11811 (2002).

  8. 8

    He, L. H. & Lemasters, J. J. FEBS Lett. 512, 1–7 (2002).

  9. 9

    Crompton, M., Virji, S. & Ward, J. M. Eur. J. Biochem. 258, 729–735 (1998).

  10. 10

    Pebay Peyroula, E. et al. Nature 426, 39–44 (2003).

  11. 11

    Waldmeier, P. C., Zimmermann, K., Qian, T., Tintelnot Blomley, M. & Lemasters, J. J. Curr. Medicinal Chem. 10, 1485–1506 (2003).

Download references

Author information


  1. Department of Biochemistry, University of Bristol, Bristol, BS8 1TD, UK

    • Andrew P. Halestrap


  1. Search for Andrew P. Halestrap in:

Corresponding author

Correspondence to Andrew P. Halestrap.

About this article

Publication history


Issue Date


Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.