PMID- 37435031 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230718 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 11 DP - 2023 TI - Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle. PG - 1212779 LID - 10.3389/fcell.2023.1212779 [doi] LID - 1212779 AB - 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. CI - Copyright (c) 2023 Castro-Sepulveda, Tunon-Suarez, Rosales-Soto, Vargas-Foitzick, Deldicque and Zbinden-Foncea. FAU - Castro-Sepulveda, Mauricio AU - Castro-Sepulveda M AD - Laboratorio de Fisiologia del Ejercicio y Metabolismo, Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile. FAU - Tunon-Suarez, Mauro AU - Tunon-Suarez M AD - Laboratorio de Fisiologia del Ejercicio y Metabolismo, Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile. FAU - Rosales-Soto, Giovanni AU - Rosales-Soto G AD - Facultad de Ciencias de la Educacion, Universidad San Sebastian, Sede Bellavista, Santiago, Chile. FAU - Vargas-Foitzick, Ronald AU - Vargas-Foitzick R AD - Laboratorio de Fisiologia del Ejercicio y Metabolismo, Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile. FAU - Deldicque, Louise AU - Deldicque L AD - Institute of Neuroscience, UCLouvain, Ottignies-Louvain-la- Neuve, Belgium. FAU - Zbinden-Foncea, Hermann AU - Zbinden-Foncea H AD - Laboratorio de Fisiologia del Ejercicio y Metabolismo, Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile. AD - Institute of Neuroscience, UCLouvain, Ottignies-Louvain-la- Neuve, Belgium. AD - Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria, Madrid, Espana. LA - eng PT - Journal Article DEP - 20230626 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC10332154 OTO - NOTNLM OT - Lipopolysaccharide OT - TAK242 OT - mitochondrial dynamics OT - mitochondrial nanotunnels OT - skeletal muscle function OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/07/12 06:42 MHDA- 2023/07/12 06:43 PMCR- 2023/01/01 CRDT- 2023/07/12 03:51 PHST- 2023/04/26 00:00 [received] PHST- 2023/06/12 00:00 [accepted] PHST- 2023/07/12 06:43 [medline] PHST- 2023/07/12 06:42 [pubmed] PHST- 2023/07/12 03:51 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 1212779 [pii] AID - 10.3389/fcell.2023.1212779 [doi] PST - epublish SO - Front Cell Dev Biol. 2023 Jun 26;11:1212779. doi: 10.3389/fcell.2023.1212779. eCollection 2023.