AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
Sci Adv
; 8(45): eabo7956, 2022 11 11.
Article
en En
| MEDLINE
| ID: mdl-36367943
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas Activadas por AMP
/
Dinámicas Mitocondriales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido