Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle

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dc.contributor.authorCastro-Sepulveda, Mauricio
dc.contributor.authorTuñón-Suárez, Mauro
dc.contributor.authorRosales-Soto, Giovanni
dc.contributor.authorVargas-Foitzick, Ronald
dc.contributor.authorDeldicque, Louise
dc.contributor.authorZbinden-Foncea, Hermann
dc.date.accessioned2024-11-28T15:23:14Z
dc.date.available2024-11-28T15:23:14Z
dc.date.issued2023-06-25
dc.description.abstractIn skeletal muscle (SkM), a reduced mitochondrial elongate phenotype is associated with several metabolic disorders like type 2 diabetes mellitus (T2DM). However, the mechanisms contributing to this reduction in mitochondrial elongate phenotype in SkM have not been fully elucidated. It has recently been shown in a SkM cell line that toll-like receptor 4 (TLR4) contributes to the regulation of mitochondrial morphology. However, this has not been investigated in human SkM. Here we found that in human SkM biopsies, TLR4 protein correlated negatively with Opa1 (pro-mitochondrial fusion protein). Moreover, the incubation of human myotubes with LPS reduced mitochondrial size and elongation and induced abnormal mitochondrial cristae, which was prevented with the co-incubation of LPS with TAK242. Finally, T2DM myotubes were found to have reduced mitochondrial elongation and mitochondrial cristae density. Mitochondrial morphology, membrane structure, and insulin-stimulated glucose uptake were restored to healthy levels in T2DM myotubes treated with TAK242. In conclusion, mitochondrial morphology and mitochondrial cristae seem to be regulated by the TLR4 pathway in human SkM. Those mitochondrial alterations might potentially contribute to insulin resistance in the SkM of patients with T2DM.
dc.identifier.citationFrontiers in Cell and Developmental Biology, Vol.11, N° 1212779 (2023) p. 1-9.
dc.identifier.doihttps://doi.org/10.3389/fcell.2023.1212779
dc.identifier.issn2296-634X
dc.identifier.orcidhttps://orcid.org/0000-0002-2270-299X
dc.identifier.orcidhttps://orcid.org/0000-0002-3085-9057
dc.identifier.orcidhttps://orcid.org/0000-0003-4466-1276
dc.identifier.orcidhttps://orcid.org/0000-0002-9643-1037
dc.identifier.urihttp://hdl.handle.net/20.500.12254/3939
dc.language.isoen
dc.publisherFrontiers Media S.A.
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectMitochondrial dynamics
dc.subjectSkeletal muscle function
dc.subjectMitochondrial nanotunnels
dc.subjectLipopolysaccharide
dc.subjectType 2 diabetes
dc.titleRegulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle
dc.typeArticle
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