Tilokani 2022 Sci Adv
Tilokani L, Russell FM, Hamilton S, Virga DM, Segawa M, Paupe V, Gruszczyk AV, Protasoni M, Tabara LC, Johnson M, Anand H, Murphy MP, Hardie DG, Polleux F, Prudent J (2022) AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology. https://doi.org/10.1126/sciadv.abo7956 |
Β» Sci Adv 8:eabo7956. PMID: 36367943 Open Access
Tilokani Lisa, Russell Fiona M, Hamilton Stevie, Virga Daniel M, Segawa Mayuko, Paupe Vincent, Gruszczyk Anja V, Protasoni Margherita, Tabara Luis-Carlos, Johnson Mark, Anand Hanish, Murphy Michael P, Hardie D Grahame, Polleux Franck, Prudent Julien (2022) Sci Adv
Abstract: 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.
β’ Bioblast editor: Plangger M
Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression
Organism: Human
Tissue;cell: Other cell lines
Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: ROX
HRR: Oxygraph-2k
2022-11