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Study of PTPC Composition during Apoptosis for Identification of Viral Protein Target
Author(s) -
VERRIER FLORENCE,
MIGNOTTE BERNARD,
JAN GWENAËL,
BRENNER CATHERINE
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1299.022
Subject(s) - voltage dependent anion channel , intermembrane space , mitochondrial intermembrane space , biology , microbiology and biotechnology , biochemistry , adenine nucleotide translocator , cytochrome c , mitochondrion , bacterial outer membrane , chemistry , escherichia coli , gene
A bstract : 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 strategiesthat 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.