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Published on: October 23, 2018
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.
Abstract:
The AMP-activated protein kinase (AMPK) is known to maintain the integrity of cellular mitochondrial networks by (i) promoting fission, (ii) inhibiting fusion, (iii) promoting recycling of damaged components via mitophagy, (iv) enhancing lysosomal biogenesis to support mitophagy, and (v) promoting biogenesis of new mitochondrial components. While the AMPK targets underlying the first three of these effects are known, a recent paper suggests that direct phosphorylation of the folliculin-interacting protein 1 (FNIP1) by AMPK may be involved in the remaining two.
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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