Similar Datasets
Project description:We found that changes in mitochondrial membrane potential or ROS generation trigger the translocation of OLA1 from mitochondria and cytoplasm to the nucleus, regulated by ERK1-mediated phosphorylation of OLA1 on Ser232/Tyr236. Subsequent phosphorylation of nuclear-OLA1 on Thre325 by ERK2 activates its function as a genetic factor regulating cellular homeostasis by modulating HDAC9 expression. Disruption of OLA1 phosphorylation blocks its nuclear translocation, compromised the expression of nuclear-encoded mitochondrial proteins, DNA damage response, and multiple stress-response-related-genes, leading to cellular dysfunction. Our findings reveal that OLA1 is a crucial component of mitonuclear response regulatory hubs essential for regulating cellular adaptation to stress.
2022-01-14 | GSE193318 | GEO
Project description:We found that changes in mitochondrial membrane potential or ROS generation trigger the translocation of OLA1 from mitochondria and cytoplasm to the nucleus, regulated by ERK1-mediated phosphorylation of OLA1 on Ser232/Tyr236. Subsequent phosphorylation of nuclear-OLA1 on Thre325 by ERK2 activates its function as a genetic factor regulating cellular homeostasis by modulating HDAC9 expression. Disruption of OLA1 phosphorylation blocks its nuclear translocation, compromised the expression of nuclear-encoded mitochondrial proteins, DNA damage response, and multiple stress-response-related-genes, leading to cellular dysfunction. Our findings reveal that OLA1 is a crucial component of mitonuclear response regulatory hubs essential for regulating cellular adaptation to stress.
2022-01-14 | GSE193317 | GEO
Project description:We found that changes in mitochondrial membrane potential or ROS generation trigger the translocation of OLA1 from mitochondria and cytoplasm to the nucleus, regulated by ERK1-mediated phosphorylation of OLA1 on Ser232/Tyr236. Subsequent phosphorylation of nuclear-OLA1 on Thre325 by ERK2 activates its function as a genetic factor regulating cellular homeostasis by modulating HDAC9 expression. Disruption of OLA1 phosphorylation blocks its nuclear translocation, compromised the expression of nuclear-encoded mitochondrial proteins, DNA damage response, and multiple stress-response-related-genes, leading to cellular dysfunction. Our findings reveal that OLA1 is a crucial component of mitonuclear response regulatory hubs essential for regulating cellular adaptation to stress.
2023-11-21 | GSE218381 | GEO
Project description:ERK-Mediated Phosphorylation of OLA1 Controls Adaptive Mitochondria to Nucleus Communication Regulating Cellular Homeostasis
| PRJNA795850 | ENA
Project description:ERK-Mediated Phosphorylation of OLA1 Controls Adaptive Mitochondria to Nucleus Communication Regulating Cellular Homeostasis [RNA-seq]
| PRJNA795852 | ENA
Project description:ERK-Mediated Phosphorylation of OLA1 Controls Adaptive Mitochondria to Nucleus Communication Regulating Cellular Homeostasis [ChIP-seq]
| PRJNA795788 | ENA
Project description:Retrograde response was widely studied in budding yeast but the main transcription factors that transmit it (RTG1,2 and 3) are not conserved in other organisms, thus it is interesting to study how communication between mitochondria and nucleus evolved in distantly related fission yeast, and which are the common aspects of this conserved pathway between yeast and higher organisms.To analyse any retrograde response in fission yeast, we inhibited the electron transport chain activity by antimycin A and studied cellular gene expression changes by microarrays. Cells treated with antimycin A in fermentative medium (YE with 3% glucose), showed the same growth rate as untreated cells, but they reached a lower biomass in stationary phase. Antimycin A treated cells consumed glucose at a faster rate and produced more ethanol, indicating that the energy metabolism was shifted even more towards fermentation. We analyzed the transcriptomes of antimycin A-treated cells to untreated control cells during early exponential growth phase (OD 0.5).
2016-11-01 | E-MTAB-4520 | biostudies-arrayexpress
Project description:BACKGROUND:The interaction of nuclear and mitochondrial genes is an essential feature in maintenance of normal cellular function. Of 82 structural subunits that make up the oxidative phosphorylation system in the mitochondria, mitochondrial DNA (mtDNA) encodes 13 subunits and rest of the subunits are encoded by nuclear DNA. Mutations in mitochondrial genes encoding the 13 subunits have been reported in a variety of cancers. However, little is known about the nuclear response to impairment of mitochondrial function in human cells. RESULTS:We isolated a Rho0 (devoid of mtDNA) derivative of a breast cancer cell line. Our study suggests that depletion of mtDNA results in oxidative stress, causing increased lipid peroxidation in breast cancer cells. Using a cDNA microarray we compared differences in the nuclear gene expression profile between a breast cancer cell line (parental Rho+) and its Rho0 derivative impaired in mitochondrial function. Expression of several nuclear genes involved in cell signaling, cell architecture, energy metabolism, cell growth, apoptosis including general transcription factor TFIIH, v-maf, AML1, was induced in Rho0 cells. Expression of several genes was also down regulated. These include phospholipase C, agouti related protein, PKC gamma, protein tyrosine phosphatase C, phosphodiestarase 1A (cell signaling), PIBF1, cytochrome p450, (metabolism) and cyclin dependent kinase inhibitor p19, and GAP43 (cell growth and differentiation). CONCLUSIONS:Mitochondrial impairment in breast cancer cells results in altered expression of nuclear genes involved in signaling, cellular architecture, metabolism, cell growth and differentiation, and apoptosis. These genes may mediate the cross talk between mitochondria and the nucleus.
| S-EPMC149409 | biostudies-literature
Project description:The endoplasmic reticulum (ER) and mitochondria form contacts that support communication between these two organelles, including synthesis and transfer of lipids, and the exchange of calcium, which regulates ER chaperones, mitochondrial ATP production, and apoptosis. Despite the fundamental roles for ER-mitochondria contacts, little is known about the molecules that regulate them. Here we report the identification of a multifunctional sorting protein, PACS-2, that integrates ER-mitochondria communication, ER homeostasis, and apoptosis. PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER. PACS-2 also controls formation of ER lipid-synthesizing centers found on mitochondria-associated membranes and ER homeostasis. However, in response to apoptotic inducers, PACS-2 translocates Bid to mitochondria, which initiates a sequence of events including the formation of mitochondrial truncated Bid, the release of cytochrome c, and the activation of caspase-3, thereby causing cell death. Together, our results identify PACS-2 as a novel sorting protein that links the ER-mitochondria axis to ER homeostasis and the control of cell fate, and provide new insights into Bid action.
| S-EPMC549619 | biostudies-literature
Project description:Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis) and the removal of damaged mitochondria by selective autophagy (mitophagy). While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM) to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1) mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2) restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3) maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4) our model suggests sources of, and stress conditions amplifying, cell-to-cell variability of mitochondrial morphology and energetic stress states. Overall, our modeling approach integrates biochemical and imaging knowledge, and presents a novel open-modeling approach to investigate how spatial and temporal mitochondrial dynamics contribute to functional homeostasis, and how subcellular organelle heterogeneity contributes to the emergence of cell heterogeneity.
| S-EPMC5217980 | biostudies-literature