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Proteolysis of adaptor protein Mmr1 during budding is necessary for mitochondrial homeostasis in Saccharomyces cerevisiae.

ABSTRACT: In yeast, mitochondria are passed on to daughter cells via the actin cable, motor protein Myo2, and adaptor protein Mmr1. They are released from the actin-myosin machinery after reaching the daughter cells. We report that Mmr1 is rapidly degraded by the ubiquitin-proteasome system in Saccharomyces cerevisiae. Redundant ubiquitin ligases Dma1 and Dma2 are responsible for Mmr1 ubiquitination. Dma1/2-mediated Mmr1 ubiquitination requires phosphorylation, most likely at S414 residue by Ste20 and Cla4. These kinases are mostly localized to the growing bud and nearly absent from mother cells, ensuring phosphorylation and ubiquitination of Mmr1 after the mitochondria enter the growing bud. In dma1Δ dma2Δ cells, transported mitochondria are first stacked at the bud-tip and then pulled back to the bud-neck. Stacked mitochondria in dma1Δ dma2Δ cells exhibit abnormal morphology, elevated respiratory activity, and increased level of reactive oxygen species, along with hypersensitivity to oxidative stresses. Collectively, spatiotemporally-regulated Mmr1 turnover guarantees mitochondrial homeostasis.

SUBMITTER: Obara K

PROVIDER: S-EPMC9010424 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Proteolysis of adaptor protein Mmr1 during budding is necessary for mitochondrial homeostasis in Saccharomyces cerevisiae.

Obara Keisuke K Yoshikawa Taku T Yamaguchi Ryu R Kuwata Keiko K Nakatsukasa Kunio K Nishimura Kohei K Kamura Takumi T

Nature communications 20220414 1

In yeast, mitochondria are passed on to daughter cells via the actin cable, motor protein Myo2, and adaptor protein Mmr1. They are released from the actin-myosin machinery after reaching the daughter cells. We report that Mmr1 is rapidly degraded by the ubiquitin-proteasome system in Saccharomyces cerevisiae. Redundant ubiquitin ligases Dma1 and Dma2 are responsible for Mmr1 ubiquitination. Dma1/2-mediated Mmr1 ubiquitination requires phosphorylation, most likely at S414 residue by Ste20 and Cla ...[more]

PMID: 35422486

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Project description:Introduction Protein corona (PCN) adsorbed on the surface of nanoparticles has brought new research perspectives for the interaction between nanoparticles and microorganisms. In this study, the responses of saccharomyces cerevisiae’ membrane lipid composition, the average length of the fatty acyl chains and the average number of unsaturation of fatty acids to ultrasound combined with nano-Fe3O4@PCN with time-limited proteolysis (nano-Fe3O4@TLP-PCN) was investigated. Methods Lipidomic data was obtained using Ultra-high performance liquid chromatography coupled with a Q-Exactive plus mass spectrometer. The membrane potential, proton motive force assay and the membrane lipid oxidation were measured using Di-BAC4(3), DISC3(5) and C11-BODIPY581/591 as the probes. Combined with the approach of feasible virtual samples generation, the back propagation artificial neural network (BP-ANN) model was adopted to establish the mapping relationship between lipids and membrane properties. Results The time-limited proteolysis targeting wheat PCN-coated Fe3O4 nanoparticles resulted in regular changes of hydrodynamic diameters, ζ-potentials, and surface hydrophobicity. In addition, with the prolongation of PCN proteolysis time, disturbances of 3 S.cerevisiae membrane characteristics, and membrane lipidomic remodeling in response to ultrasound+ nano-Fe3O4@PCN were observed. The analysis of relative importance which followed revealed that ergosterol, phosphatidylserine, and phosphatidylinositol phosphate had the greatest influence on membrane potential. For membrane lipid oxidation, ceramide, phosphatidylethanolamine, and sitosterol ester contribute 16.2, 14.9, and 13.1%, respectively. The relative contributions of six lysolecithins to the dissipation of proton motive force remained limited. Discussion An adaptation mechanism of cell membrane to proteolyzed PCN, wherein lipidome remodeling could preserved functional membrane phenotypes was revealed. Furthermore, it is highlighted that the relative importances of SiE, Cer, PE and PIP in determining membrane potential, PMF dissipation and membrane lipid oxidation by establishing FVSG-BP-ANN model.

Project description:Core histone proteins are essential for packaging the genomic DNA into chromatin in all eukaryotes. Since multiple genes encode these histone proteins, there is potential for generating more histones than what is required for chromatin assembly. The positively charged histones have a very high affinity for negatively charged molecules such as DNA, and any excess of histone proteins results in deleterious effects on genomic stability and cell viability. Hence, histone levels are known to be tightly regulated via transcriptional, posttranscriptional and posttranslational mechanisms. We have previously elucidated the posttranslational regulation of histone protein levels by the ubiquitin-proteasome pathway involving the E2 ubiquitin conjugating enzymes Ubc4/5 and the HECT (Homologous to E6-AP C-Terminus) domain containing E3 ligase Tom1 in the budding yeast. Here we report the identification of four additional E3 ligases containing the RING (Really Interesting New Gene) finger domains that are involved in the ubiquitylation and subsequent degradation of excess histones in yeast. These E3 ligases are Pep5, Snt2 as well as two previously uncharacterized Open Reading Frames (ORFs) YKR017C and YDR266C that we have named Hel1 and Hel2 (for Histone E3 Ligases) respectively. Mutants lacking these E3 ligases are sensitive to histone overexpression as they fail to degrade excess histones and accumulate high levels of endogenous histones on histone chaperones. Co-immunoprecipitation assays showed that these E3 ligases interact with the major E2 enzyme Ubc4 that is involved in the degradation related ubiquitylation of histones. Using mutagenesis we further demonstrate that the RING domains of Hel1, Hel2 and Snt2 are required for histone regulation. Lastly, mutants corresponding to Hel1, Hel2 and Pep5 are sensitive to replication inhibitors. Overall, our results highlight the importance of posttranslational histone regulatory mechanisms that employ multiple E3 ubiquitin ligases to ensure excess histone degradation and thus contribute to the maintenance of genomic stability.

Dataset Information

Proteolysis of adaptor protein Mmr1 during budding is necessary for mitochondrial homeostasis in Saccharomyces cerevisiae.

Publications

Proteolysis of adaptor protein Mmr1 during budding is necessary for mitochondrial homeostasis in Saccharomyces cerevisiae.

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