Mitofusion is required for MOTS-c induced GLUT4 translocation
Khushwant S Bhullar1,2, Nan Shang1, Evan Kerek2
1Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Scientific Reports
|July 13, 2021
Summary
Mitochondrial peptide MOTS-c enhances glucose uptake by promoting mitochondrial fusion, not just biogenesis. This discovery reveals a new pathway linking mitochondrial dynamics to metabolic improvements.
Area of Science:
- Metabolic research
- Mitochondrial biology
- Molecular medicine
Background:
- MOTS-c is a mitochondrial peptide known to improve insulin resistance and obesity.
- The precise mechanisms underlying MOTS-c's pharmacological actions are not fully understood.
- Previous studies suggest MOTS-c may influence mitochondrial function and cold adaptation.
Purpose of the Study:
- To investigate the role of MOTS-c in mitochondrial biogenesis and dynamics.
- To elucidate the molecular pathways connecting MOTS-c to improved glucose uptake.
- To determine if mitochondrial fusion is involved in MOTS-c's metabolic effects.
Main Methods:
- Treatment of mammalian cells with MOTS-c.
- Assessed protein levels of mitochondrial biogenesis markers (TFAM, COX4, NRF1).
- Flow cytometry with MitoTracker Green to quantify mitochondria.
- Measured protein levels of mitochondrial fusion GTPases (OPA1, MFN2).
- Inhibited GTPases using TNFα or siRNA to assess impact on GLUT4 translocation and glucose uptake.
Main Results:
- MOTS-c increased markers of mitochondrial biogenesis but decreased overall mitochondrial count.
- MOTS-c significantly upregulated OPA1 and MFN2, key proteins for mitochondrial fusion.
- Inhibition of OPA1/MFN2 or MFN2 specifically blocked MOTS-c-induced GLUT4 translocation and glucose uptake.
- This highlights a novel link between mitochondrial fusion and MOTS-c's metabolic benefits.
Conclusions:
- MOTS-c promotes mitochondrial biogenesis and subsequent mitochondrial fusion.
- Mitofusion is a critical step in MOTS-c's mechanism for enhancing glucose uptake.
- This study reveals a new pathway linking mitochondrial dynamics to MOTS-c's therapeutic potential in metabolic disorders.
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