Lysophospholipase PNPLA7 is a critical checkpoint of phosphatidylcholine catabolism and turnover for skeletal muscle homeostasis
Year: 2026
Type: article
Abstract: Current evidence suggests that disturbed phosphatidylcholine (PC) turnover causes skeletal muscle dysfunction. However, the enzyme that converts lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC), an irreversible checkpoint in PC catabolism, in skeletal muscle has remained unidentified. Here we show that PNPLA7, a patatin-like phospholipase isoform, is responsible for this process. Pnpla7 deletion in myoblasts impedes the conversion of LPC to GPC and then to choline. Quadriceps muscles in global Pnpla7-deficient mice display thinner muscle fibers with aberrant mitochondrial morphology, reduced endurance capacity, and decreased expression of genes related to fatty acid β-oxidation, mitochondrial functions, and slow-twitch fibers with age. These abnormalities are preceded by alterations in phospholipid composition, with decreases in docosahexaenoic acid-containing PC and mitochondrial cardiolipin. Moreover, skeletal muscle-specific Pnpla7 deficiency results in muscle phenotypes similar to its global deficiency. Identification of the lysophospholipase PNPLA7 aids further understanding of the role of PC turnover in skeletal muscle homeostasis.
Source: Cell Reports
Institutions: Center for Disease Biology and Integrative Medicine, The University of Tokyo, The University of Tokyo, Tokyo Metropolitan Institute of Medical Science, National Institute of Biomedical Innovation, Health and Nutrition, Institute for Protein Research, The University of Osaka, The University of Osaka, Osaka Metropolitan University, Institute for Advanced Biosciences, Keio University, Keio University, Keio University Human Biology-Microbiome-Quantum Research Center, Japan Agency for Medical Research and Development
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W7214949553