Peptido-Targeting of the Mitochondrial Transition Pore Complex for Therapeutic Apoptosis Induction

Aurelien      Deniaud; Johan      Hoebeke; Jean-Paul      Briand; Sylviane      Muller; Etienne      Jacotot; Catherine      Brenner

doi:10.2174/138161206779010530

Abstract

The permeability transition pore (PTPC), a polyprotein complex, participates in the mitochondrial homeostasis as well as in the mitochondrial phase of the intrinsic pathway of apoptosis. It integrates multiple death signals including alterations of the intracellular milieu, translocation of pro-apoptotic members of the Bax/Bcl-2 family, p53, and viral proteins. As a consequence, PTPC can act as a coordinator of the pro-apoptotic mitochondrial membrane permeabilization process and the release of pro-apoptotic intermembrane space proteins into the cytosol. Moreover, the deregulation of PTPC has been involved in several major human pathologies such as cancer, neurodegeneration, ischemia/reperfusion, aging, as well as hepatotoxicity. Therefore, PTPC has emerged as a promising potential therapeutic target. Here, we will review the current knowledge concerning the two opposite functions of the PTPC and its implication in various pathologies. We will discuss the possibility to target this complex with peptides to modulate apoptosis in an innovative therapeutic perspective.

Keywords: ATP cell content, inner mitochondrial membrane (IM), Cancer, Ischemic reperfusion injury, voltage-dependent anion channel (VDAC)

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