ArticleNature communications2022
Enrichment of the exocytosis protein STX4 in skeletal muscle remediates peripheral insulin resistance and alters mitochondrial dynamics via Drp1.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Review
- TAS1R3 Regulates GTPase Signaling in Human Skeletal Muscle Cells for Glucose Uptake.International journal of molecular sciences · 2025Article
- Characterization of Adipocyte-Derived Extracellular Vesicle Secretion Using a CD63-GFP Reporter Mouse Model In Vivo and In Vitro.Journal of visualized experiments : JoVE · 2025Article
- STX4 Is Indispensable for Mitochondrial Homeostasis in Skeletal Muscle.Journal of cachexia, sarcopenia and muscle · 2025Article
- Pulmonary mitochondrial DNA release and activation of the cGAS-STING pathway in Lethal Stx12 knockout mice.Cell communication and signaling : CCS · 2025Article
- DRP1, fission and apoptosis.Cell death discovery · 2025Review
- Syntaxin 4-enhanced plasma membrane repair is independent of dysferlin in skeletal muscle.American journal of physiology. Cell physiology · 2025Article
- Mitochondrial bioenergetics dysfunction in T2DM: linking oxidative stress to insulin resistance.Frontiers in endocrinology · 2025Review
- Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway.Nature communications · 2024Article
- Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression.International journal of molecular sciences · 2024Review
- A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin.International journal of molecular sciences · 2023Article
- Article
- The Complex Interplay between Imbalanced Mitochondrial Dynamics and Metabolic Disorders in Type 2 Diabetes.Cells · 2023Review
- MitoSNARE Assembly and Disassembly Factors Regulate Basal Autophagy and Aging inInternational journal of molecular sciences · 2023Article
- Age-Related Dysfunction in Proteostasis and Cellular Quality Control in the Development of Sarcopenia.Cells · 2023Review
- Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis.Frontiers in endocrinology · 2022Article
- The Effect of Aerobic Exercise on the Oxidative Capacity of Skeletal Muscle Mitochondria in Mice with Impaired Glucose Tolerance.Journal of diabetes research · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Mitochondrial dysfunction is implicated in skeletal muscle insulin resistance. Syntaxin 4 (STX4) levels are reduced in human diabetic skeletal muscle, and global transgenic enrichment of STX4 expression improves insulin sensitivity in mice. Here, we show that transgenic skeletal muscle-specific STX4 enrichment (skmSTX4tg) in mice reverses established insulin resistance and improves mitochondrial function in the context of diabetogenic stress. Specifically, skmSTX4tg reversed insulin resistance caused by high-fat diet (HFD) without altering body weight or food consumption. Electron microscopy of wild-type mouse muscle revealed STX4 localisation at or proximal to the mitochondrial membrane. STX4 enrichment prevented HFD-induced mitochondrial fragmentation and dysfunction through a mechanism involving STX4-Drp1 interaction and elevated AMPK-mediated phosphorylation at Drp1 S637, which favors fusion. Our findings challenge the dogma that STX4 acts solely at the plasma membrane, revealing that STX4 localises at/proximal to and regulates the function of mitochondria in muscle. These results establish skeletal muscle STX4 enrichment as a candidate therapeutic strategy to reverse peripheral insulin resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.