Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle
In 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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1212779/full |
| _version_ | 1827916256577060864 |
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| author | Mauricio Castro-Sepulveda Mauro Tuñón-Suárez Giovanni Rosales-Soto Ronald Vargas-Foitzick Louise Deldicque Hermann Zbinden-Foncea Hermann Zbinden-Foncea Hermann Zbinden-Foncea |
| author_facet | Mauricio Castro-Sepulveda Mauro Tuñón-Suárez Giovanni Rosales-Soto Ronald Vargas-Foitzick Louise Deldicque Hermann Zbinden-Foncea Hermann Zbinden-Foncea Hermann Zbinden-Foncea |
| author_sort | Mauricio Castro-Sepulveda |
| collection | DOAJ |
| description | In 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. |
| first_indexed | 2024-03-13T03:11:27Z |
| format | Article |
| id | doaj.art-fc604178342641c79e90d35a521778b8 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T03:11:27Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-fc604178342641c79e90d35a521778b82023-06-26T12:14:50ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-06-011110.3389/fcell.2023.12127791212779Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscleMauricio Castro-Sepulveda0Mauro Tuñón-Suárez1Giovanni Rosales-Soto2Ronald Vargas-Foitzick3Louise Deldicque4Hermann Zbinden-Foncea5Hermann Zbinden-Foncea6Hermann Zbinden-Foncea7Laboratorio de Fisiología del Ejercicio y Metabolismo, Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, ChileLaboratorio de Fisiología del Ejercicio y Metabolismo, Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, ChileFacultad de Ciencias de la Educación, Universidad San Sebastián, Sede Bellavista, Santiago, ChileLaboratorio de Fisiología del Ejercicio y Metabolismo, Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, ChileInstitute of Neuroscience, UCLouvain, Ottignies-Louvain-la- Neuve, BelgiumLaboratorio de Fisiología del Ejercicio y Metabolismo, Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, ChileInstitute of Neuroscience, UCLouvain, Ottignies-Louvain-la- Neuve, BelgiumFacultad de Ciencias de la Salud, Universidad Francisco de Vitoria, Madrid, EspañaIn 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1212779/fullmitochondrial dynamicsskeletal muscle functionmitochondrial nanotunnelsLipopolysaccharideTAK242type 2 diabetes |
| spellingShingle | Mauricio Castro-Sepulveda Mauro Tuñón-Suárez Giovanni Rosales-Soto Ronald Vargas-Foitzick Louise Deldicque Hermann Zbinden-Foncea Hermann Zbinden-Foncea Hermann Zbinden-Foncea Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle Frontiers in Cell and Developmental Biology mitochondrial dynamics skeletal muscle function mitochondrial nanotunnels Lipopolysaccharide TAK242 type 2 diabetes |
| title | Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
| title_full | Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
| title_fullStr | Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
| title_full_unstemmed | Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
| title_short | Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
| title_sort | regulation of mitochondrial morphology and cristae architecture by the tlr4 pathway in human skeletal muscle |
| topic | mitochondrial dynamics skeletal muscle function mitochondrial nanotunnels Lipopolysaccharide TAK242 type 2 diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1212779/full |
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