ArticleThe Journal of clinical investigation2021
Defective lysosome reformation during autophagy causes skeletal muscle disease.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 85 citations in OpenAlex.
- Exercise-induced lysosomal adaptations in skeletal muscle.Sports medicine and health science · 2026Review
- The power of five - inositol polyphosphate 5-phosphatase gene mutations at the intersection of development and disease.FEBS letters · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- INPP5K limits PtdIns (4,5)P2 accumulation in CD19 microclusters and restrains CD19 co-receptor membrane proximity and BCR-proximal signaling in B cells.Frontiers in immunology · 2026Article
- Metformin protects retinal ganglion cells in a preclinical model of retinal ischemia/reperfusion injury and stabilizes visual field in diabetic patients with glaucoma.Cell death discovery · 2025Article
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Identification of new candidates regulating autophagy-dependent midgut degradation in Drosophila melanogaster.Cell death discovery · 2025Article
- Transcriptional regulation of autophagy in skeletal muscle stem cells.Disease models & mechanisms · 2025Review
- Skeletal Muscle Mitochondrial and Autophagic Dysregulation Are Modifiable in Spinal Muscular Atrophy.Journal of cachexia, sarcopenia and muscle · 2025Article
- Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.Bioscience reports · 2025Review
- Tetrandrine induces muscle atrophy involving ROS-mediated inhibition of Akt and FoxO3.Molecular medicine (Cambridge, Mass.) · 2024Article
- Whole-transcriptome sequencing revealed the ceRNA regulatory network during the proliferation and differentiation of goose myoblast.Poultry science · 2024Article
- Enhanced protective effect of whey protein fermented withFood science and biotechnology · 2024Article
- Exploring the Link Between Autophagy-Lysosomal Dysfunction and Early Heterotopic Ossification in Tendons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The interactions of subcellular organelles in pulmonary fibrosis induced by carbon black nanoparticles: a comprehensive review.Archives of toxicology · 2024Review
- Proteome-based molecular subtyping and therapeutic target prediction in gastric cancer.Molecular oncology · 2024Article
- Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.American journal of physiology. Cell physiology · 2024Article
- A conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.Autophagy · 2024Article
- Recent progresses in the late stages of autophagy.Cell insight · 2024Review
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The regulation of autophagy-dependent lysosome homeostasis in vivo is unclear. We showed that the inositol polyphosphate 5-phosphatase INPP5K regulates autophagic lysosome reformation (ALR), a lysosome recycling pathway, in muscle. INPP5K hydrolyzes phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] to phosphatidylinositol 4-phosphate [PI(4)P], and INPP5K mutations cause muscular dystrophy by unknown mechanisms. We report that loss of INPP5K in muscle caused severe disease, autophagy inhibition, and lysosome depletion. Reduced PI(4,5)P2 turnover on autolysosomes in Inpp5k-/- muscle suppressed autophagy and lysosome repopulation via ALR inhibition. Defective ALR in Inpp5k-/- myoblasts was characterized by enlarged autolysosomes and the persistence of hyperextended reformation tubules, structures that participate in membrane recycling to form lysosomes. Reduced disengagement of the PI(4,5)P2 effector clathrin was observed on reformation tubules, which we propose interfered with ALR completion. Inhibition of PI(4,5)P2 synthesis or expression of WT INPP5K but not INPP5K disease mutants in INPP5K-depleted myoblasts restored lysosomal homeostasis. Therefore, bidirectional interconversion of PI(4)P/PI(4,5)P2 on autolysosomes was integral to lysosome replenishment and autophagy function in muscle. Activation of TFEB-dependent de novo lysosome biogenesis did not compensate for loss of ALR in Inpp5k-/- muscle, revealing a dependence on this lysosome recycling pathway. Therefore, in muscle, ALR is indispensable for lysosome homeostasis during autophagy and when defective is associated with muscular dystrophy.
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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 Socratic graph.