The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target

Author(s): Anne-Sophie Belzacq, Catherine Brenner.

Journal Name: Current Drug Targets

Volume 4 , Issue 7 , 2003

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Abstract:

Identification of new targets is of utmost importance for the development of efficient apoptosis-modulating drugs. This has become possible from the unraveling of the basic apoptosis mechanisms and notably, from the demonstration of the mitochondrial membrane permeabilization as a central rate-limiting step of numerous models of cell death. Indeed, molecular and pharmacological studies revealed that the adenine nucleotide translocator (ANT) could be a therapeutic target. First, ANT is a bi-functional protein. It mediates the exchange of cytosolic ADP and mitochondrial ATP, and contributes to apoptosis via its capacity to become a lethal pore. Second, both ANT functions are under the control of the (anti)-oncogenes from the Bax / Bcl-2 family, and third, agents as diverse as proteins, lipids, ions, pro-oxidants or chemotherapeutic agents directly modulate the pore-forming activity of ANT. Here, we will review the mode of apoptosis induction by various classes of chemotherapeutic agents, which all influence directly ANT pro-apoptotic function. Hopefully, this will yield several clues to the modulation of apoptosis from a therapeutic perspective.

Keywords: apoptosis, chemotherapy, liposome, mitochondrion, oncogene

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Article Details

VOLUME: 4
ISSUE: 7
Year: 2003
Page: [517 - 524]
Pages: 8
DOI: 10.2174/1389450033490867
Price: $58

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