ArticleCell metabolism2014
Lipin-1 regulates autophagy clearance and intersects with statin drug effects in skeletal muscle.
Article in Cell metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed.
- Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.JCI insight · 2018Trial
- Quercetin alleviates statin-induced myopathy in adult male rats: insights into the role of oxidative stress, apoptosis, and autophagy-related gene expression (LC3 and LAMP2).Journal of molecular histology · 2026Article
- Lipin1 restores nNOS sarcolemmal localization and improves fatigue resistance in Duchenne muscular dystrophy.American journal of physiology. Cell physiology · 2026Article
- Skeletal muscle-specific deficiency of Rab geranylgeranyl transferase beta subunit induces myopathy and exacerbates the symptoms caused by HMG-CoA reductase deficiency in mice.Molecular metabolism · 2026Article
- Multi-omics reveal phosphatidic acid phosphatases modify Niemann-Pick type C disease severity.iScience · 2026Article
- Statins promote muscle metabolic danger and NLRP3-mediated myopathy via lower protein-prenylation and YAP.Science advances · 2026Article
- Physical exercise in metabolic myopathies at risk of rhabdomyolysis: a feasible approach or an unavoidable hazard?European journal of applied physiology · 2025Review
- Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.Advances in biological regulation · 2025Review
- Phosphatidate phosphatase Lipin1 alters mitochondria-associated endoplasmic reticulum membranes (MAMs) homeostasis: effects which contribute to the development of diabetic encephalopathy.Journal of neuroinflammation · 2025Article
- Inhibiting de novo lipogenesis identifies a therapeutic vulnerability in therapy-resistant colorectal cancer.Redox biology · 2025Article
- Adult-Onset Episodic Rhabdomyolysis in a Patient With a Heterozygous Lipin 1 (LPIN1) Mutation: A Case Report.Cureus · 2025Article
- Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.Journal of lipid research · 2025Article
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Mitochondrial dynamics at the intersection of macrophage polarization and metabolism.Frontiers in immunology · 2025Review
- Insights into phosphatidic acid phosphatase and its potential role as a therapeutic target.Advances in biological regulation · 2025Review
- TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning.Autophagy reports · 2024Article
- Architecture and function of yeast phosphatidate phosphatase Pah1 domains/regions.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Review
- Proteomic Profiling of Hindlimb Skeletal Muscle Disuse in a Murine Model of Sepsis.Critical care explorations · 2024Article
- Exploring lipin1 as a promising therapeutic target for the treatment of Duchenne muscular dystrophy.Journal of translational medicine · 2024Article
- Fluvastatin-induced myofibrillar damage is associated with elevated ROS, and impaired fatty acid oxidation, and is preceded by mitochondrial morphological changes.Scientific reports · 2024Article
47 more citing papers are in PubMed but not listed here.
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Abstract
LPIN1 encodes lipin-1, a phosphatidic acid phosphatase (PAP) enzyme that catalyzes the dephosphorylation of phosphatidic acid to form diacylglycerol. Homozygous LPIN1 gene mutations cause severe rhabdomyolysis, and heterozygous LPIN1 missense mutations may promote statin-induced myopathy. We demonstrate that lipin-1-related myopathy in the mouse is associated with a blockade in autophagic flux and accumulation of aberrant mitochondria. Lipin-1 PAP activity is required for maturation of autolysosomes, through its activation of the protein kinase D (PKD)-Vps34 phosphatidylinositol 3-kinase signaling cascade. Statin treatment also reduces PKD activation and autophagic flux, which are compounded by diminished mammalian target of rapamycin (mTOR) abundance in lipin-1-haploinsufficent and -deficient muscle. Lipin-1 restoration in skeletal muscle prevents myonecrosis and statin toxicity in vivo, and activated PKD rescues autophagic flux in lipin-1-deficient cells. Our findings identify lipin-1 PAP activity as a component of the macroautophagy pathway and define the basis for lipin-1-related myopathies.
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