title: Study of PTPC composition during apoptosis for identification of viral protein target.
abstract: The permeability transition pore complex (PTPC), a mitochondrial polyprotein complex, has been previously described to be involved in the control of mitochondrial membrane permeabilization (MMP) during chemotherapy-induced apoptosis. PTPC may contain proteins from both mitochondrial membranes [e.g., voltage-dependent anion channel (VDAC), PRAX-1, peripheral benzodiazepine receptor (PBR), adenine nucleotide translocator (ANT)], from cytosol (e.g., hexokinase II, glycerol kinase), from matrix [e.g., cyclophilin D (CypD)], and from intermembrane space (e.g., creatine kinase). PTPC may also interact with tumor suppressor proteins (i.e., Bax and Bid), oncoprotein homologues of Bcl-2 and some viral proteins, which can regulate apoptosis induced by pore opening. ANT and VDAC are the target of numerous pro-apoptotic MMP inducers. However, the precise composition of PTPC as well as the respective role of each PTPC component represent major issues in the understanding MMP process. Using several experimental strategies that combine co-immunoprecipitation, proteomics, and functional tests with proteoliposomes, we and others have been able to characterize some of the intra/inter-PTPC protein interactions leading to a better understanding of the process of MMP. In addition, this approach could identify new putative members and regulators of PTPC pro-apoptotic function and new targets of viral protein involved in the modulation of apoptosis during infection.
authors.affiliation: CNRS FRE 2445, Université de Versailles/St. Quentin, 45, avenue des Etats-Unis, 78035 Versailles, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Verrier
authors.forename: Bernard
authors.initials: B
authors.lastname: Mignotte
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Jan
authors.forename: Catherine
authors.initials: C
authors.lastname: Brenner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D007473:Ion Channels / Q000502:physiology; D008928:Mitochondria / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D010539:Permeability; D018272:Porins / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology*; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D018272:Porins; D014764:Viral Proteins; D050994:Voltage-Dependent Anion Channels