Dynamic evolution of the adenine nucleotide translocase interactome during chemotherapy-induced apoptosis

摘要: The mitochondrial permeability transition pore complex (PTPC) is involved in the control of membrane permeabilization during apoptosis, necrosis and autophagy. Indeed, adenine nucleotide translocator (ANT) voltage-dependent anion channel (VDAC), two major components PTPC, are targets a variety proapoptotic inducers. Using co-immunoprecipitation proteomic analysis, we identified some interacting partners ANT several normal tissues human cancer cell lines. During chemotherapy-induced these interactions were constant (e.g. ANT-VDAC), whereas others changed strongly concomitantly with dissipation transmembrane potential until nuclear degradation occurred Bax, Bcl-2, subunits respiratory chain, subunit phosphatase PP2A, phospholipase PLC β 4 IP3 receptor). In addition, glutathione-S-transferase (GST) interacts tissue, colon carcinoma cells vitro. This interaction lost apoptosis induction, suggesting that GST behaves as an endogenous repressor PTPC opening. Thus, connected to proteins well from other organelles such endoplasmic reticulum forming dynamic polyprotein complex. Changes within this interactome coordinate lethal response induction.