2016A Trindade Microbial Cell Advanced Pub

Mitochondrial outer membrane permeabilization is a key event in apoptosis processes leading to the release of lethal factors. We have previously shown that absence of the ADP/ATP carrier (AAC) proteins (yeast orthologues of mammalian ANT proteins) increased the resistance of yeast cells to acetic acid, preventing MOMP and the release of cytochrome c from mitochondria during acetic acid induced apoptosis. On the other hand, deletion of POR1 (yeast voltage-dependent anion channel VDAC) increased the sensitivity of yeast cells to acetic acid. In the present work, we aimed to further characterize the role of yeast VDAC in acetic acid induced apoptosis and assess if it functionally interacts with AAC proteins. We found that the sensitivity to acetic acid resulting from POR1 deletion is completely abrogated by the absence of AAC proteins, and propose that Por1p acts as a negative regulator of acetic acid induced cell death by a mechanism dependent of AAC proteins, by acting on AAC dependent cytochrome c release. Moreover, we show that Por1p has a role in mitochondrial fusion that, contrary to its role in apoptosis, is not affected by the absence of AAC, and demonstrate that mitochondrial network fragmentation is not sufficient to induce release of cytochrome c or sensitivity to acetic acid induced apoptosis. This work enhances our understanding on cytochrome c release during cell death, which may be relevant in pathological scenarios where MOMP is compromised. VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast Dário Trindade 1,2 , Clara Pereira 3,4 , Susana R. Chaves 1 , Stéphen Manon 2 , Manuela Côrte-Real 1 and Maria João Sousa 1, * 1 Centro de Biologia Molecular e Ambiental (CBMA), Departamento de Biologia, Universidade do Minho, Campus de Gualtar, 4710057 Braga, Portugal. 2 Institut de Biochimie et de Génétique Cellulaires (IBGC), UMR5095 CNRS & Université de Bordeaux, 1 Rue de Camille Saint-Saëns, 33077 Bordeaux, France. 3 I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal. 4 IBMC-Institute for Molecular and Cell Biology, University of Porto, Porto, 4200-465, Portugal. * Corresponding Author: Maria João Sousa, Departamento de Biologia, Universidade do Minho, Campus de Gualtar; 4710-057 Braga, Portugal; Tel: +3 512 536 01545; E-mail: [email protected]