ArticleCell communication and signaling : CCS2022
Endoplasmic reticulum stress downregulates PGC-1α in skeletal muscle through ATF4 and an mTOR-mediated reduction of CRTC2.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
- Exercise-induced modulation of the unfolded protein response: a therapeutic avenue for muscle wasting disorders.Journal of physiology and biochemistry · 2026Review
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- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- The mTOR signaling pathway mediates the phenotypic switch between adipocytes and osteocytes in mice with obesity-related osteoporosis.European journal of medical research · 2025Article
- Nanoparticle-mediated targeting of PGC-1α reveals critical metabolic pathways in bladder cancer metastasis.Communications biology · 2025Article
- The PERK/ATF4 pathway is required for metabolic reprogramming and progressive lung fibrosis.JCI insight · 2025Article
- Prepregnancy Obesity Reprograms Offspring Skeletal Muscle Fibre Transition Through H3K9me3.Journal of cachexia, sarcopenia and muscle · 2025Article
- Palmitate potentiates the SMAD3-PAI-1 pathway by reducing nuclear GDF15 levels.Cellular and molecular life sciences : CMLS · 2025Article
- Protective effects of Salubrinal against HFrontiers in pharmacology · 2025Article
- Dual roles of mTOR in skeletal muscle adaptation: coordinating hypertrophic and mitochondrial biogenesis pathways for exercise-induced chronic disease management.Frontiers in medicine · 2025Article
- PPARβ/δ upregulates the insulin receptor β subunit in skeletal muscle by reducing lysosomal activity and EphB4 levels.Cell communication and signaling : CCS · 2024Article
- Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4.Cellular and molecular life sciences : CMLS · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease.Journal of translational medicine · 2023Review
- Biological functions of CRTC2 and its role in metabolism-related diseases.Journal of cell communication and signaling · 2023Review
- The Role ofInternational journal of molecular sciences · 2023Article
- PGC-1α in osteoarthritic chondrocytes: From mechanism to target of action.Frontiers in pharmacology · 2023Review
- Article
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6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPeroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) downregulation in skeletal muscle contributes to insulin resistance and type 2 diabetes mellitus. Here, we examined the effects of endoplasmic reticulum (ER) stress on PGC-1α levels in muscle and the potential mechanisms involved.
methodsThe human skeletal muscle cell line LHCN-M2 and mice exposed to different inducers of ER stress were used.
resultsPalmitate- or tunicamycin-induced ER stress resulted in PGC-1α downregulation and enhanced expression of activating transcription factor 4 (ATF4) in human myotubes and mouse skeletal muscle. Overexpression of ATF4 decreased basal PCG-1α expression, whereas ATF4 knockdown abrogated the reduction of PCG-1α caused by tunicamycin in myotubes. ER stress induction also activated mammalian target of rapamycin (mTOR) in myotubes and reduced the nuclear levels of cAMP response element-binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), a positive modulator of PGC-1α transcription. The mTOR inhibitor torin 1 restored PCG-1α and CRTC2 protein levels. Moreover, siRNA against S6 kinase, an mTORC1 downstream target, prevented the reduction in the expression of CRTC2 and PGC-1α caused by the ER stressor tunicamycin.
conclusionsCollectively, these findings demonstrate that ATF4 and the mTOR-CRTC2 axis regulates PGC-1α transcription under ER stress conditions in skeletal muscle, suggesting that its inhibition might be a therapeutic target for insulin resistant states. Video Abstract.
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