Academic Journal
AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
| Τίτλος: | AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology. |
|---|---|
| Συγγραφείς: | Tilokani L; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Russell FM; Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK., Hamilton S; Department of Neuroscience, Columbia University, New York, NY 10032, USA., Virga DM; Department of Neuroscience, Columbia University, New York, NY 10032, USA., Segawa M; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Paupe V; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Gruszczyk AV; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Protasoni M; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Tabara LC; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Johnson M; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Anand H; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK., Murphy MP; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK.; Department of Medicine, University of Cambridge, Cambridge, UK., Hardie DG; Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK., Polleux F; Department of Neuroscience, Columbia University, New York, NY 10032, USA., Prudent J; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK. |
| Πηγή: | Science advances [Sci Adv] 2022 Nov 11; Vol. 8 (45), pp. eabo7956. Date of Electronic Publication: 2022 Nov 11. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| Ιατρικοί όροι (MeSH): | AMP-Activated Protein Kinases*/metabolism , Mitochondrial Dynamics*, Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Membrane Proteins/metabolism ; Mammals/metabolism ; Animals ; Mice ; Phosphorylation |
| Περίληψη: | Mitochondria are dynamic organelles that undergo membrane remodeling events in response to metabolic alterations to generate an adequate mitochondrial network. Here, we investigated the function of mitochondrial fission regulator 1-like protein (MTFR1L), an uncharacterized protein that has been identified in phosphoproteomic screens as a potential AMP-activated protein kinase (AMPK) substrate. We showed that MTFR1L is an outer mitochondrial membrane-localized protein modulating mitochondrial morphology. Loss of MTFR1L led to mitochondrial elongation associated with increased mitochondrial fusion events and levels of the mitochondrial fusion protein, optic atrophy 1. Mechanistically, we show that MTFR1L is phosphorylated by AMPK, which thereby controls the function of MTFR1L in regulating mitochondrial morphology both in mammalian cell lines and in murine cortical neurons in vivo. Furthermore, we demonstrate that MTFR1L is required for stress-induced AMPK-dependent mitochondrial fragmentation. Together, these findings identify MTFR1L as a critical mitochondrial protein transducing AMPK-dependent metabolic changes through regulation of mitochondrial dynamics. |
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| Grant Information: | R35 NS127232 United States NS NINDS NIH HHS; R01 NS107483 United States NS NINDS NIH HHS; United Kingdom WT_ Wellcome Trust; MC_UU_00015/7 United Kingdom MRC_ Medical Research Council; MC_UU_00028/5 United Kingdom MRC_ Medical Research Council |
| Substance Nomenclature: | EC 2.7.11.31 (AMP-Activated Protein Kinases) 0 (Mitochondrial Proteins) 0 (Membrane Proteins) |
| Entry Date(s): | Date Created: 20221111 Date Completed: 20221115 Latest Revision: 20260526 |
| Update Code: | 20260526 |
| PubMed Central ID: | PMC9651865 |
| DOI: | 10.1126/sciadv.abo7956 |
| PMID: | 36367943 |
| Βάση Δεδομένων: | MEDLINE |
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