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.