{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Puri R"],"funding":["Intramural NIH HHS","U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke"],"pagination":["3645"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6692330"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Chronic mitochondrial stress associates with major neurodegenerative diseases. Recovering stressed mitochondria constitutes a critical step of mitochondrial quality control and thus energy maintenance in early stages of neurodegeneration. Here, we reveal Mul1-Mfn2 pathway that maintains neuronal mitochondrial integrity under stress conditions. Mul1 deficiency increases Mfn2 activity that triggers the first phasic mitochondrial hyperfusion and also acts as an ER-Mito tethering antagonist. Reduced ER-Mito coupling leads to increased cytoplasmic Ca<sup>2+</sup> load that activates calcineurin and induces the second phasic Drp1-dependent mitochondrial fragmentation and mitophagy. Overexpressing Mfn2, but not Mfn1, mimics Mul1-deficient phenotypes, while expressing PTPIP51, an ER-Mito anchoring"],"journal":["Nature communications"],"pubmed_title":["Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts."],"pmcid":["PMC6692330"],"funding_grant_id":["NIH ZIA NS003029","ZIA NS003029","NIH ZIA NS002946","ZIA NS002946"],"pubmed_authors":["Lin MY","Sheng ZH","Puri R","Huang N","Cheng XT"],"additional_accession":[]},"is_claimable":false,"name":"Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts.","description":"Chronic mitochondrial stress associates with major neurodegenerative diseases. Recovering stressed mitochondria constitutes a critical step of mitochondrial quality control and thus energy maintenance in early stages of neurodegeneration. Here, we reveal Mul1-Mfn2 pathway that maintains neuronal mitochondrial integrity under stress conditions. Mul1 deficiency increases Mfn2 activity that triggers the first phasic mitochondrial hyperfusion and also acts as an ER-Mito tethering antagonist. Reduced ER-Mito coupling leads to increased cytoplasmic Ca<sup>2+</sup> load that activates calcineurin and induces the second phasic Drp1-dependent mitochondrial fragmentation and mitophagy. Overexpressing Mfn2, but not Mfn1, mimics Mul1-deficient phenotypes, while expressing PTPIP51, an ER-Mito anchoring","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Aug","modification":"2025-04-04T19:04:11.709Z","creation":"2019-08-20T07:05:16Z"},"accession":"S-EPMC6692330","cross_references":{"pubmed":["31409786"],"doi":["10.1038/s41467-019-11636-5"]}}