VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast
Authors:Dário Trindade1,2, Clara Pereira3,4, Susana R. Chaves1, Stéphen Manon2, Manuela Côrte-Real1 and Maria João Sousa1
doi: 10.15698/mic2016.10.533
Volume 3, pp. 500 to 510, published 25/08/2016.
1 Centro de Biologia Molecular e Ambiental (CBMA), Departamento de Biologia, Universidade do Minho, Campus de Gualtar, 4710-057 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.
Keywords:
AAC, Por1, mitochondria, cytochrome c, acetic acid, apoptosis.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Dário Trindade, Clara Pereira, Susana R. Chaves, Stéphen Manon, Manuela Côrte-Real and Maria João Sousa (2016). VDAC regulates AAC-mediated apoptosis and cytochrome c release in yeast. Microbial Cell 3(10): 500-510. doi: 10.15698/mic2016.10.533
© 2016 Trindade et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
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.