Skip to main content
SpringerLink
Log in

AMPK and insulin control the switch between mitochondrial hitchhiking of Pink1 mRNA and mitophagy in neurons

  • Research Briefing
  • Published:

From Nature Metabolism

View current issue Submit your manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: Inhibition of AMPK untethers Pink1 mRNA from mitochondria in a SYNJ2BP phosphorylation-dependent manner.

References

  1. Misgeld, T. & Schwarz, T. L. Mitostasis in neurons: Maintaining mitochondria in an extended cellular architecture. Neuron 96, 651–666 (2017). A review article that presents the challenging task neurons face to support mitochondrial protein homeostasis in distal regions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Harbauer, A. B. et al. Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy. Neuron 110, 1516–1531 (2022). This paper reports our original finding of Pink1 mRNA hitchhiking on neuronal mitochondria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hees, J. T. & Harbauer, A. B. Metabolic regulation of mitochondrial protein biogenesis from a neuronal perspective. Biomolecules 12, 1–16 (2022). A review article that presents the interplay between translational and transcriptional regulation of mitochondrial protein synthesis.

    Article  Google Scholar 

  4. Han, R., Liu, Y., Li, S., Li, X. J. & Yang, W. PINK1-PRKN mediated mitophagy: differences between in vitro and in vivo models. Autophagy 19, 1396–1405 (2023). A review article that discusses the current evidence of PINK1-mediated mitophagy in vitro and in the brain in various animal models.

    Article  CAS  PubMed  Google Scholar 

  5. Zhao, N. et al. Apolipoprotein E4 impairs neuronal insulin signaling by trapping insulin receptor in the endosomes. Neuron 96, 115–129 (2017). This paper reports the effect of ApoE4 on insulin receptor trafficking in neurons.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s42255-024-01006-x

  • Springer Nature Limited

Search

Navigation