2026-10-01 東京大学
膜リン脂質の新陳代謝の乱れは骨格筋の恒常性を損なう
＜関連情報＞
- https://www.u-tokyo.ac.jp/content/400297241.pdf
- https://www.cell.com/cell-reports/fulltext/S2211-1247(26)01081-8
リゾホスホリパーゼPNPLA7は、骨格筋の恒常性維持におけるホスファチジルコリンの異化と代謝回転の重要なチェックポイントである Lysophospholipase PNPLA7 is a critical checkpoint of phosphatidylcholine catabolism and turnover for skeletal muscle homeostasis
Shoya Matsumoto ∙ Heeyoon Seo ∙ Yoshitaka Taketomi ∙ … ∙ Tetsuya Hirabayashi ∙ Sumito Ogawa ∙ Makoto Murakami
Cell Reports Published:September 30, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.118003
Highlights
- Global or muscle-specific loss of PNPLA7 leads to skeletal muscle degeneration
- Myoblast PNPLA7 deletion impedes the phosphatidylcholine-choline metabolic cycle
- PNPLA7-deficient mice display thinner muscle fibers with reduced endurance capacity
- Mitochondrial dysfunction by PNPLA7 deficiency is rescued by DHA or choline
Summary
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.
