The adenine nucleotide translocator: a new potential chemotherapeutic target.
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.
Belzacq
Anne-Sophie
AS
Centre National de la Recherche Scientifique, UMR 6022, Université de Technologie de Compiègne, 60205 Compiègne, France.
Brenner
Catherine
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D000226:Mitochondrial ADP, ATP Translocases