PXD045665 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Loss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice |
Description | Objective: 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-01-26 |
AnnouncementXML | Submission_2024-01-26_08:06:07.750.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Laura Liesinger |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-09-25 09:36:05 | ID requested | |
⏵ 1 | 2024-01-26 08:06:08 | announced | |
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 affiliation | Faculty 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 email | ruth.birner-gruenberger@tuwien.ac.at |
lab head | |
Laura Liesinger |
contact affiliation | Faculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria; |
contact email | laura.liesinger@tuwien.ac.at |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045665
- Label: PRIDE project
- Name: Loss of lysosomal acid lipase results in mitochondrial dysfunction and fiber switch in skeletal muscles of mice