ArticleNature metabolism2024
Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Organelle-anchored translation factories: the roles of neuronal RNA-binding protein condensates in organizing local protein synthesis in neurological diseases.Protein & cell · 2026Review
- Trans-activator of transcription-pre-B-cell leukemia transcription factor 1 alleviates Alzheimer's disease by reducing neuronal insulin resistance and restoring energy homeostasis.Neural regeneration research · 2026Article
- Time- and Region-Specific Effects of Intranasal Insulin on Oxidative Stress Parameters in the Rat Brain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A human-specific microRNA controls the timing of excitatory synaptogenesis.Nature communications · 2026Article
- Co-translational protein targeting to mitochondria in the context of co-translational protein maturation.Protein science : a publication of the Protein Society · 2026Review
- The Interaction Between Insulin Resistance and Neuroinflammation in the Brain and Its Impact on Diabetic Encephalopathy.Biology · 2026Review
- ALKBH3 m1A Demethylase Deficiency Reduces Alzheimer's Amyloid-β Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synaptojanin-2-binding protein ameliorates oxidative stress, neuroinflammation and depression-like behaviors via SYNJ2/PIPRedox biology · 2026Article
- Transcriptome predictors of second breast events in ductal carcinoma in situ: a case‒control study including Black and White women.Breast cancer research : BCR · 2026Article
- Mitochondrial dynamics in neurodevelopment and neurodevelopmental disorders.Nature reviews. Neuroscience · 2026Review
- The endoplasmic reticulum in mitochondrial protein targeting: A neuronal perspective on organelle crosstalk.Protein science : a publication of the Protein Society · 2026Review
- Diverse intracellular trafficking of insulin analogs by machine learning-based colocalization and diffusion analysis.iScience · 2026Article
- A central role for PINK1 in governing local mitochondrial biogenesis and degradation in neurons.Cellular and molecular life sciences : CMLS · 2026Review
- Review
- Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Vesicle-coupled mRNA transport and translation govern intracellular organelle networking.EMBO reports · 2026Review
- A unified mechanism for mitochondrial damage sensing in PINK1-Parkin-mediated mitophagy.The EMBO journal · 2026Article
- Curcumin improves diabetic vascular aging rats and high glucose-induced cells aging by promoting mitophagy.3 Biotech · 2025Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization of PTEN-induced kinase 1 (PINK1) requires transport of Pink1 messenger RNA (mRNA) by tethering it to the mitochondrial surface. Here, we report that inhibition of AMP-activated protein kinase (AMPK) by activation of the insulin signalling cascade prevents Pink1 mRNA binding to mitochondria. Mechanistically, AMPK phosphorylates the RNA anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site that is necessary for its interaction with the RNA-binding protein SYNJ2. Notably, loss of mitochondrial Pink1 mRNA association upon insulin addition is required for PINK1 protein activation and its function as a ubiquitin kinase in the mitophagy pathway, thus placing PINK1 function under metabolic control. Induction of insulin resistance in vitro by the key genetic Alzheimer risk factor apolipoprotein E4 retains Pink1 mRNA at the mitochondria and prevents proper PINK1 activity, especially in neurites. Our results thus identify a metabolic switch controlling Pink1 mRNA localization and PINK1 activity via insulin and AMPK signalling in neurons and propose a mechanistic connection between insulin resistance and mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.