AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology

Lisa Tilokani, Fiona M. Russell, Stevie Hamilton, Daniel M. Virga, Mayuko Segawa, Vincent Paupe, Anja V. Gruszczyk, Margherita Protasoni, Luis-Carlos Tabara, Mark Johnson, Hanish Anand, Michael P. Murphy, D. Grahame Hardie, Franck Polleux, Julien Prudent (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
103 Downloads (Pure)


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.

Original languageEnglish
Article numbereabo7956
Number of pages20
JournalScience Advances
Issue number45
Publication statusPublished - 11 Nov 2022


  • Animals
  • Mice
  • Phosphorylation
  • AMP-Activated Protein Kinases/metabolism
  • Mitochondrial Dynamics
  • Mitochondria/metabolism
  • Mitochondrial Proteins/genetics
  • Membrane Proteins/metabolism
  • Mammals/metabolism

ASJC Scopus subject areas

  • General


Dive into the research topics of 'AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology'. Together they form a unique fingerprint.

Cite this