Cited by 60Mitochondrial Function and PathologyAutophagy in Disease and TherapyMetabolism, Diabetes, and Cancer

AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology

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Tilokani, Lisa, Russell, Fiona M., Hamilton, Stevie, Virga, Daniel M., Segawa, Mayuko, Paupe, Vincent, Gruszczyk, Anja V., Protasoni, Margherita +7 more·2022·Science Advances

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.

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Authors
Tilokani, L., Russell, F. M., Hamilton, S., Virga, D. M., Segawa, M., Paupe, V., Gruszczyk, A. V., Protasoni, M., Tabara, L.-C., Johnson, M., Anand, H., Murphy, M. P., Hardie, D. G., Polleux, F., & Prudent, J.
Affiliations
  • University of Cambridge (GB)
  • University of Dundee (GB)
  • Columbia University (US)
  • Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Hills Road, CB2 0XY Cambridge, UK.
Corresponding author
  • Russell, Fiona M.
  • Hamilton, Stevie
  • Virga, Daniel M.
  • Prudent, Julien
Venue
Science Advances
Published
2022-11-11
Volume
8
Issue
45
Pages
eabo7956-eabo7956
ISSN
2375-2548 (ISSN-L)
OpenAlex
W4308916364
Cited by
60
References
7
Citations by year
2026: 17 · 2025: 16 · 2024: 15 · 2023: 12
FWCI
3.51
Type
journal article
Language
en
Open access
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cc-by
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  • Science Advances (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (204766/Z/16/Z)
  • Medical Research Council (MC_UU_00028/5, MC_UU_00015/7)
  • National Institute of Neurological Disorders and Stroke (R01NS107483, R35NS127232)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
AMPK, AMPK phosphorylation, mitochondrial morphology, mitochondrial fission, mitochondrial fusion, optic atrophy 1, mitochondrial dynamics, mitochondrial outer membrane, cortical neurons, metabolic stress, mitochondrial fragmentation
MeSH terms
Animals, Mammals, Membrane Proteins, Mitochondria, Phosphorylation, Mitochondrial Proteins, Mice, AMP-Activated Protein Kinases, Mitochondrial Dynamics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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