A window into intracellular events in myositis through subcellular proteomics
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Le résumé fourni par la source
OBJECTIVE AND DESIGN: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of inflammatory muscle disorders of unknown etiology. It is postulated that mitochondrial dysfunction and protein aggregation in skeletal muscle contribute to myofiber degeneration. However, molecular pathways that lead to protein aggregation in skeletal muscle are not well defined. SUBJECTS: Here we have isolated membrane-bound organelles (e.g., nuclei, mitochondria, sarcoplasmic/endoplasmic reticulum, Golgi apparatus, and plasma membrane) from muscle biopsies of normal (n = 3) and muscle disease patients (n = 11). Of the myopathy group, 10 patients displayed mitochondrial abnormalities (IIM (n = 9); mitochondrial myopathy (n = 1)), and one IIM patient did not show mitochondrial abnormalities (polymyositis). METHODS: Global proteomic analysis was performed using an Orbitrap Fusion mass spectrometer. Upon unsupervised clustering, normal and mitochondrial myopathy muscle samples clustered separately from IIM samples. RESULTS: We have confirmed previously known protein alterations in IIM and identified several new ones. For example, we found differential expression of (i) nuclear proteins that control cell division, transcription, RNA regulation, and stability, (ii) ER and Golgi proteins involved in protein folding, degradation, and protein trafficking in the cytosol, and (iii) mitochondrial proteins involved in energy production/metabolism and alterations in cytoskeletal and contractile machinery of the muscle. CONCLUSIONS: Our data demonstrates that molecular alterations are not limited to protein aggregations in the cytosol (inclusions) and occur in nuclear, mitochondrial, and membrane compartments of IIM skeletal muscle.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A window into intracellular events in myositis through subcellular proteomics
- Date Crossref
- 31/01/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Toledo Department of Exercise and Rehabilitative Sciences pays non établi dans la noticeUniversité ou école supérieure
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McGill University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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McGill University Health Centre pays non établi dans la noticeÉtablissement de santé
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Jewish General Hospital pays non établi dans la noticeÉtablissement de santé
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University of Manitoba Department of Biochemistry and Medical Genetics pays non établi dans la noticeUniversité ou école supérieure
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Lady Davis Institute for Medical Research Segal Cancer Proteomics Centre pays non établi dans la noticeStructure de recherche
Department of Exercise and Rehabilitative Sciences — University of Toledo, Department of Medicine — McGill University et McGill University Health Centre, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.