Role of mitochondria in cell senescence-induced death
of yeast Saccharomyces cerevisiae

N.A. Bocharova1,3, D.A Knorre2,3, F.F. Severin2.3
1Department of Bioengineering and Bioinformatics, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia
2Belozersky Institute of Physico-Chemical Biology, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia
3Institute of Mitoengineering, Moscow State University, Leninskye Gory, 1, Moscow, 119991, Russia

It is known that mammalian cells with heavily damaged DNA and/or mitotic apparatus may undergo long term cell cycle arrest. This arrest is called senescence and, unlike G0/G1 delay (quiescence), eventually leads either to cell death or cancerous transformation. It was shown that S. cerevisiae cells arrested with non-replicated telomeres undergo senescence-like cell death which can be rescued by either antioxidant or rapamycin treatment [1]. Importantly, the same treatments prolong the survival of senescent mammalian cells. We asked first whether this type of yeast cell death is specific to telomere replication defect or can be induced by other factors arresting cells in the division phase. It appeared that long-term mitotic arrest induced by cdc15-1 and cdc26delta mutations in Anaphase-Promoting Complex (APC) displays the same features: causes rapamycin- and antioxidant-sensitive cell death.
Why the prolonged arrest causes death? Unlike higher cells, yeast lack specialized proteins (p53, etc.) which trigger cell senescence-dependent apoptosis. One possible reason for the arrest-induced death can be multiplication of mitochondria in the absence of nuclear DNA replication, resulting in the imbalance between mitochondrial and nuclear-encoded proteins in mitochondria. Supporting this, we found that mitochondrial translational inhibitor chloramphenicol or rho0 mutation rescue the senescence-induced death while mutations in mitochondrial retrograde signaling reduce the survival. Together it suggests a novel conservative pathway for senescence-induced cell death.
This work was supported by RFBR grant 09-04-01704 and Grant of President of Russian Federation MK-4628.2009.4

[1] Qi H, Chen Y Fu X, Lin C-P, Zheng XFS, et al. (2008) TOR Regulates Cell Death Induced by Telomere Dysfunction in Budding Yeast. PLoS ONE 3(10): e3520. doi:10.1371/journal.pone.0003520

Homo Sapiens Liberatus Workshop, Moscow State University, May 2010