Peptido-targeting of the mitochondrial transition pore complex for therapeutic apoptosis induction.
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.
Deniaud
Aurélien
A
CNRS UMR 8159, Université de Versailles / St Quentin, 45, avenue des Etats-Unis, 78035 Versailles, France.
Hoebeke
Johan
J
Briand
Jean-Paul
JP
Muller
Sylviane
S
Jacotot
Etienne
E
Brenner
Catherine
C
D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016503:Drug Delivery Systems; D006706:Homeostasis; D006801:Humans; D008107:Liver Diseases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D018384:Oxidative Stress; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010455:Peptides