title: Mitochondrial retrograde signaling inhibits the survival during prolong S/G2 arrest in Saccharomyces cerevisiae.
abstract: Cell senescence is dependent on the arrest in cell cycle. Here we studied the role of mitochondrial retrograde response signaling in yeast cell survival under a prolonged arrest. We have found that, unlike G1, long-term arrest in mitosis or S phase results in a loss of colony-forming abilities. Consistent with previous observations, loss of mitochondrial DNA significantly increased the survival of arrested cells. We found that this was because the loss increases the duration of G1 phase. Unexpectedly, retrograde signaling, which is typically triggered by a variety of mitochondrial dysfunctions, was found to be a negative regulator of the survival after the release from S-phase arrest induced by the telomere replication defect. Deletion of retrograde response genes decreased the arrest-induced death in such cells, whereas deletion of negative regulator of retrograde signaling MKS1 had the opposite effect. We provide evidence that these effects are due to alleviation of the strength of the S-phase arrest.
authors.affiliation: Faculty of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
authors.forename: Anna N
authors.initials: AN
authors.lastname: Zyrina
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Maksim I
authors.initials: MI
authors.lastname: Sorokin
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Sviatoslav S
authors.initials: SS
authors.lastname: Sokolov
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Knorre
authors.affiliation: Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
mesh_terms: D016923:Cell Death; D016922:Cellular Senescence; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D015966:Gene Expression Regulation, Fungal; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D004271:DNA, Fungal; D004272:DNA, Mitochondrial; C080921:MKS1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: Rtg pathway; cell cycle arrest; mitochondria; retrograde signaling; telomere dysfunction