AMPK directly phosphorylates the mitochondrial protein SYNJ2BP to facilitate its interaction with the RNA-binding protein SYNJ2a, which transports Pink1 mRNA into neurites. AMPK inhibition downstream of insulin signalling untethers Pink1 mRNA from neuronal mitochondria and favours PINK1-dependent mitophagy in neurons. ApoE4-induced insulin receptor internalization reverses the process by stabilizing Pink1 mRNA binding to neuronal mitochondria.
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References
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This is a summary of: Hees, J. T. et al. Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons. Nat. Metab. https://doi.org/10.1038/s42255-024-01007-w (2024).
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AMPK and insulin control the switch between mitochondrial hitchhiking of Pink1 mRNA and mitophagy in neurons. Nat Metab 6, 392–393 (2024). https://doi.org/10.1038/s42255-024-01006-x
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DOI: https://doi.org/10.1038/s42255-024-01006-x
