ArticleMolecular metabolism2019
Phosphatidylserine decarboxylase is critical for the maintenance of skeletal muscle mitochondrial integrity and muscle mass.
Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Targeting mitochondrial phosphatidylethanolamine alters mitochondrial metabolism and proliferation in hepatocellular carcinoma.Oncogenesis · 2025Article
- Fatty liver reexamined choline and mitochondrial toxin amelioration.World journal of biological chemistry · 2025Review
- Chronic alcohol intake elicits distinct multi-omic profiles in the liverbioRxiv : the preprint server for biology · 2025Article
- Exploring the molecular mechanism of EGCG in preventing obesity-induced precocious puberty based on serum metabolomics and molecular docking.Frontiers in nutrition · 2025Article
- SLMO transfers phosphatidylserine between the outer and inner mitochondrial membrane in Drosophila.PLoS biology · 2024Article
- Biochemistry and Diseases Related to the Interconversion of Phosphatidylcholine, Phosphatidylethanolamine, and Phosphatidylserine.International journal of molecular sciences · 2024Review
- Lipid peroxidation does not mediate muscle atrophy induced by PSD deficiency.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms of Modulation of Mitochondrial Architecture.Biomolecules · 2023Review
- Phosphatidylserine decarboxylase downregulation in uric acid‑induced hepatic mitochondrial dysfunction and apoptosis.MedComm · 2023Article
- Amino Acid Profiles in Older Adults with Frailty: Secondary Analysis from MetaboFrail and BIOSPHERE Studies.Metabolites · 2023Article
- Phosphoethanolamine cytidylyltransferase ameliorates mitochondrial function and apoptosis in hepatocytes in T2DM in vitro.Journal of lipid research · 2023Article
- Chicken or Egg? Mitochondrial Phospholipids and Oxidative Stress in Disuse-Induced Skeletal Muscle Atrophy.Antioxidants & redox signaling · 2023Review
- The metabolic landscape in chronic rotator cuff tear reveals tissue-region-specific signatures.Journal of cachexia, sarcopenia and muscle · 2022Article
- Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: results from the BIOSPHERE study.GeroScience · 2021Article
- Article
- Current Pharmacological Strategies for Duchenne Muscular Dystrophy.Frontiers in cell and developmental biology · 2021Review
- The Crucial Roles of Phospholipids in Aging and Lifespan Regulation.Frontiers in physiology · 2021Review
- Older adults with sarcopenia have distinct skeletal muscle phosphodiester, phosphocreatine, and phospholipid profiles.Aging cell · 2020Article
- Reign in the membrane: How common lipids govern mitochondrial function.Current opinion in cell biology · 2020Review
- Knockdown of TFAM in Tumor Cells Retarded Autophagic Flux through Regulating p53 Acetylation and PISD Expression.Cancers · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePhosphatidylethanolamine (PtdEtn) is a major phospholipid in mammals. It is synthesized via two pathways, the CDP-ethanolamine pathway in the endoplasmic reticulum and the phosphatidylserine (PtdSer) decarboxylase (PSD) pathway in the mitochondria. While the CDP-ethanolamine pathway is considered the major route for PtdEtn synthesis in most mammalian tissues, little is known about the importance of the PSD pathway in vivo, especially in tissues enriched with mitochondria such as skeletal muscle. Therefore, we aimed to examine the role of the mitochondrial PSD pathway in regulating PtdEtn homeostasis in skeletal muscle in vivo.
methodsTo determine the functional significance of this pathway in skeletal muscle in vivo, an adeno-associated viral vector approach was employed to knockdown PSD expression in skeletal muscle of adult mice. Muscle lipid and metabolite profiling was performed using mass spectrometry.
resultsPSD knockdown disrupted muscle phospholipid homeostasis leading to an ∼25% reduction in PtdEtn and an ∼45% increase in PtdSer content. This was accompanied by the development of a severe myopathy, evident by a 40% loss in muscle mass as well as extensive myofiber damage as shown by increased DNA synthesis and central nucleation. In addition, PSD knockdown caused marked accumulation of abnormally appearing mitochondria that exhibited severely disrupted inner membrane integrity and reduced OXPHOS protein content.
conclusionsThe PSD pathway has a significant role in maintaining phospholipid homeostasis in adult skeletal muscle. Moreover, PSD is essential for maintenance of mitochondrial integrity and skeletal muscle mass.
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