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.
Highlights
Mechanisms of mutual coordination between nuclear DNA replication and mitochondria functioning are still an opened question
Several studies showed that replication of mitochondrial DNA occurs at all stages of cell cycle [1, 2] and arresting cells in cell cycle does not prevent mtDNA replication [3, 4]
We found that the loss of mitochondrial DNA increases the survival of yeast cells by increasing the duration of G1 phase regardless of Rtgpathway activation, whereas Rtg signaling affects the survival in the S-phase
Summary
Mechanisms of mutual coordination between nuclear DNA replication and mitochondria functioning are still an opened question. Several studies showed that replication of mitochondrial DNA (mtDNA) occurs at all stages of cell cycle [1, 2] and arresting cells in cell cycle does not prevent mtDNA replication [3, 4]. There are evidences of reciprocal regulation between mitochondria and cell cycle controlling machinery. It was shown that the main cyclin-dependent kinase (yeast Cdk1) controls the assembly of TOM complex to accommodate for the increased energy demand during S-phase [5]. The structure of mitochondrial network in some cell types is changing to reflect the requirements of a specific cell cycle stage [6]. Several works pointed at a possible existence of the mitochondria-dependent checkpoints [7,8,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
