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PXD045665

PXD045665 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLoss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice
DescriptionObjective: Lysosomal acid lipase (LAL) is the only enzyme known to hydrolyze cholesteryl esters (CE) and triacylglycerols in lysosomes at an acidic pH. Despite the importance of lysosomal hydrolysis in skeletal muscle (SM), research in this area is limited. We hypothesized that LAL may play an important role in SM development, function, and metabolism as a result of lipid and/or carbohydrate metabolism disruptions. Results: Mice with systemic LAL deficiency (Lal-/-) had markedly lower SM mass, cross-sectional area, and Feret diameter despite unchanged proteolysis or protein synthesis markers in all SM examined. In addition, Lal-/- SM showed increased total cholesterol and CE concentrations, especially during fasting and maturation. Regardless of increased glucose uptake, expression of the slow oxidative fiber marker MYH7 was markedly increased in Lal-/-SM, indicating a fiber switch from glycolytic, fast-twitch fibers to oxidative, slow-twitch fibers. Proteomic analysis of the oxidative and glycolytic parts of the SM confirmed the transition between fast- and slow-twitch fibers, consistent with the decreased Lal-/- muscle size due to the “fiber paradox”. Decreased oxidative capacity and ATP concentration were associated with reduced mitochondrial function of Lal-/- SM, particularly affecting oxidative phosphorylation, despite unchanged structure and number of mitochondria. Impairment in muscle function was reflected by increased exhaustion in the treadmill peak effort test in vivo. Conclusion: We conclude that whole-body loss of LAL is associated with a profound remodeling of the muscular phenotype, manifested by fiber type switch and a decline in muscle mass, most likely due to dysfunctional mitochondria and impaired energy metabolism, at least in mice.
HostingRepositoryPRIDE
AnnounceDate2024-01-26
AnnouncementXMLSubmission_2024-01-26_08:06:07.750.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLaura Liesinger
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-25 09:36:05ID requested
12024-01-26 08:06:08announced
Publication List
Akhmetshina A, Bianco V, Bradi, ć I, Korbelius M, Pirchheim A, Kuentzel KB, Eichmann TO, Hinteregger H, Kolb D, Habisch H, Liesinger L, Madl T, Sattler W, Radovi, ć B, Sedej S, Birner-Gruenberger R, Vuji, ć N, Kratky D, Loss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice. Mol Metab, 79():101869(2024) [pubmed]
10.1016/j.molmet.2023.101869;
Keyword List
submitter keyword: muscle proteomics,LAL, LAL deficiency, energy metabolism, Lal-deficient mouse
Contact List
Ruth Birner-Gruenberger
contact affiliationFaculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria; BiotechMed-Graz, 8010 Graz, Austria;
contact emailruth.birner-gruenberger@tuwien.ac.at
lab head
Laura Liesinger
contact affiliationFaculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria;
contact emaillaura.liesinger@tuwien.ac.at
dataset submitter
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