title: VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria.
abstract: Voltage-dependent anion channels (VDACs) are expressed in three isoforms, with common channeling properties and different roles in cell survival. We show that VDAC1 silencing potentiates apoptotic challenges, whereas VDAC2 has the opposite effect. Although all three VDAC isoforms are equivalent in allowing mitochondrial Ca(2+) loading upon agonist stimulation, VDAC1 silencing selectively impairs the transfer of the low-amplitude apoptotic Ca(2+) signals. Co-immunoprecipitation experiments show that VDAC1, but not VDAC2 and VDAC3, forms complexes with IP(3) receptors, an interaction that is further strengthened by apoptotic stimuli. These data highlight a non-redundant molecular route for transferring Ca(2+) signals to mitochondria in apoptosis.
authors: Department of Biomedical Sciences, University of Padova and CNR Neuroscience Institute, Padua, Italy.
authors: D
authors: D
authors: De Stefani
authors: A
authors: A
authors: Bononi
authors: A
authors: A
authors: Romagnoli
authors: A
authors: A
authors: Messina
authors: V
authors: V
authors: De Pinto
authors: P
authors: P
authors: Pinton
authors: R
authors: R
authors: Rizzuto
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047468:Immunoprecipitation; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D006861:Hydrogen Peroxide; D050995:Voltage-Dependent Anion Channel 1; D002118:Calcium