AMPK promotes lysosomal and mitochondrial biogenesis via folliculin:FNIP1

Jordana B Freemantle1, D Grahame Hardie1

  • 1Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom.

Life Metabolism
|August 25, 2023
PubMed

Insights

AMP-activated protein kinase (AMPK) maintains mitochondrial networks by regulating fission, fusion, and mitophagy. New research suggests AMPK directly phosphorylates folliculin-interacting protein 1 (FNIP1), potentially controlling lysosomal and mitochondrial biogenesis.

Area of Science:

  • Cellular Biology
  • Mitochondrial Dynamics
  • Molecular Signaling

Background:

  • AMP-activated protein kinase (AMPK) is crucial for cellular energy homeostasis and mitochondrial network maintenance.
  • AMPK influences mitochondrial integrity through processes including fission, fusion, and mitophagy.
  • Known AMPK targets explain its role in fission, fusion inhibition, and mitophagy, but not lysosomal or mitochondrial biogenesis.

Purpose of the Study:

  • To investigate the role of AMP-activated protein kinase (AMPK) in regulating mitochondrial biogenesis and lysosomal function.
  • To explore the potential involvement of folliculin-interacting protein 1 (FNIP1) as a direct AMPK target in mitochondrial maintenance.

Main Methods:

  • Investigated AMPK signaling pathways.
  • Utilized phosphorylation assays to determine direct interactions.
  • Examined the impact of AMPK-FNIP1 interaction on mitochondrial and lysosomal biogenesis.

Main Results:

  • AMPK directly phosphorylates folliculin-interacting protein 1 (FNIP1).
  • This phosphorylation event is suggested to be involved in promoting lysosomal biogenesis.
  • The AMPK-FNIP1 interaction may also play a role in the biogenesis of new mitochondrial components.

Conclusions:

  • AMPK's role in maintaining mitochondrial integrity extends to regulating lysosomal and mitochondrial biogenesis.
  • Direct phosphorylation of FNIP1 by AMPK is a potential mechanism for these effects.
  • This finding expands our understanding of AMPK's comprehensive control over mitochondrial health.

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