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
Current Drug Targets
Title: The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target
Volume: 4 Issue: 7
Author(s): Anne-Sophie Belzacq and Catherine Brenner
Affiliation:
Keywords: apoptosis, chemotherapy, liposome, mitochondrion, oncogene
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.
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Cite this article as:
Belzacq Anne-Sophie and Brenner Catherine, The Adenine Nucleotide Translocator: A New Potential Chemotherapeutic Target, Current Drug Targets 2003; 4 (7) . https://dx.doi.org/10.2174/1389450033490867
DOI https://dx.doi.org/10.2174/1389450033490867 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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