The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
Lipin-1 Regulates Autophagy Clearance and Intersects with Statin Drug Effects in Skeletal Muscle
Open accessAbstract
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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“In this model, myopathy/myositis could be aggravated by co-administration of statins, whereas both lipin-1 deficiency and statins were found to attenuate autolysosome maturation.”
From Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management (2015) · cites this paper as [104]
In the citing paper
“Only recently, mice with genetically induced deficiency of lipin-1, a phosphatidic acid phosphatase, were shown to develop myopathy/myositis that was associated with impaired autophagy and the presence of abnormal mitochondria.104”
From Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management (2015) · cites this paper as [104]
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Cites
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“The underlying mechanisms for statin myotoxicity are not understood, but there is evidence that underlying genetic variations may predispose some individuals (Link et al., 2008; Mangravite et al., 2013; Needham andMastaglia, 2014).”
Termination of autophagy and reformation of lysosomes regulated by mTOR
Yu, L., McPhee, C. K., Zheng, L., Mardones, G. A., Rong, Y., Peng, J., Mi, N., Zhao, Y., Liu, Z., Wan, F., et al. (2010) · Nature · doi:10.1038/nature09076 · Cited by 1,544
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mTOR Complex 1 Regulates Lipin 1 Localization to Control the SREBP Pathway
Peterson, T. R., Sengupta, S., Harris, T. E., Carmack, A. E., Kang, S. A., Balderas, E., Guertin, D. A., Madden, K. L., Carpenter, A. E., Finck, B. N., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.034 · Cited by 1,293
Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
He, C., Bassik, M. C., Moresi, V., Sun, K., Wei, Y., Zou, Z., An, Z., Loh, J., Fisher, J., Sun, Q., et al. (2012) · Nature · doi:10.1038/nature10758 · Cited by 1,136
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The interplay between cell signalling and the mevalonate pathway in cancer
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Statin-Induced Myopathy Is Associated with Mitochondrial Complex III Inhibition
Schirris, T. J. J., Renkema, G. H., Ritschel, T., Voermans, N. C., Bilos, A., van Engelen, B. G. M., Brandt, U., Koopman, W. J. H., Beyrath, J., Rodenburg, R. J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.002 · Cited by 235
Metadata
- Authors
- Zhang, P., Verity, M. A., & Reue, K.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Reue, Karen
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 20
- Issue
- 2
- Pages
- 267-279
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4170588
- OpenAlex
- W2052660293
- Cited by
- 166
- References
- 60
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 20 · 2023: 10 · 2022: 10 · 2021: 18 · 2020: 17 · 2019: 15 · 2018: 16 · 2017: 8 · 2016: 11 · 2015: 19 · 2014: 4
- FWCI
- 10.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (P01 HL090553, P01 HL028481, P20RR16475)
- National Science Foundation (0920663, MCB 0455318, DBI 0521587, EPS 0236913)
- Kansas State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- LPIN1, autophagy, statin-induced myopathy, skeletal muscle, phosphatidate phosphohydrolase, protein kinase D, mTOR, mitochondrial accumulation, muscle necrosis, rhabdomyolysis, macroautophagy, diacylglycerol
- MeSH terms
- Animals, Autophagy, Cell Line, Creatine Kinase, Female, Lipids, Mice, Inbred BALB C, Microtubule-Associated Proteins, Mitochondria, Nuclear Proteins, Phosphatidate Phosphatase, Protein Kinase C, Muscle, Skeletal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mice, Haploinsufficiency, Class III Phosphatidylinositol 3-Kinases, TOR Serine-Threonine Kinases
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