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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332154/ https://www.ncbi.nlm.nih.gov/pubmed/37435031 http://dx.doi.org/10.3389/fcell.2023.1212779 |
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author | Castro-Sepulveda, Mauricio Tuñón-Suárez, Mauro Rosales-Soto, Giovanni Vargas-Foitzick, Ronald Deldicque, Louise Zbinden-Foncea, Hermann |
author_facet | Castro-Sepulveda, Mauricio Tuñón-Suárez, Mauro Rosales-Soto, Giovanni Vargas-Foitzick, Ronald Deldicque, Louise Zbinden-Foncea, Hermann |
author_sort | Castro-Sepulveda, Mauricio |
collection | PubMed |
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 TAK(242). 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 TAK(242). 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. |
format | Online Article Text |
id | pubmed-10332154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103321542023-07-11 Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle Castro-Sepulveda, Mauricio Tuñón-Suárez, Mauro Rosales-Soto, Giovanni Vargas-Foitzick, Ronald Deldicque, Louise Zbinden-Foncea, Hermann Front Cell Dev Biol Cell and Developmental Biology 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 TAK(242). 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 TAK(242). 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. Frontiers Media S.A. 2023-06-26 /pmc/articles/PMC10332154/ /pubmed/37435031 http://dx.doi.org/10.3389/fcell.2023.1212779 Text en Copyright © 2023 Castro-Sepulveda, Tuñón-Suárez, Rosales-Soto, Vargas-Foitzick, Deldicque and Zbinden-Foncea. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Castro-Sepulveda, Mauricio Tuñón-Suárez, Mauro Rosales-Soto, Giovanni Vargas-Foitzick, Ronald Deldicque, Louise Zbinden-Foncea, Hermann Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle |
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 | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332154/ https://www.ncbi.nlm.nih.gov/pubmed/37435031 http://dx.doi.org/10.3389/fcell.2023.1212779 |
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