ArticleJournal of cell communication and signaling2021
Lactate regulates autophagy through ROS-mediated activation of ERK1/2/m-TOR/p-70S6K pathway in skeletal muscle.
Article in Journal of cell communication and signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- UHPLC-MS based metabolomics study of the ErZhi formula on skeletal muscle against osteosarcopenia focusing on energy metabolism.Animal models and experimental medicine · 2026Article
- Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma.Molecular biomedicine · 2026Article
- Lactylation in colorectal cancer: Unveiling novel mechanisms in metabolism, progression and therapeutic targeting.Clinical and translational medicine · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Spatial heterogeneity of lactylation: insights into gene expression, metabolism, and lactate transport in human embryonic stem cells.Biology open · 2026Article
- Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments.International journal of molecular sciences · 2025Review
- Research advances of lactylation modification in breast cancer.Discover oncology · 2025Review
- Exercise-driven cellular autophagy: A bridge to systematic wellness.Journal of advanced research · 2025Review
- Lactate promotes longevity through redox-driven lipid remodeling inbioRxiv : the preprint server for biology · 2025Article
- The reciprocal effects of autophagy and the Warburg effect in pancreatic ductal adenocarcinoma: an in vitro study.Medical oncology (Northwood, London, England) · 2025Article
- A first-in-class selective inhibitor of ERK1/2 and ERK5 overcomes drug resistance with a single-molecule strategy.Signal transduction and targeted therapy · 2025Article
- Recycle, repair, recover: the role of autophagy in modulating skeletal muscle repair and post-exercise recovery.Bioscience reports · 2025Review
- Article
- Polyphenols and exercise in autophagy regulation: potential benefits for cancer management and healthspan.Frontiers in nutrition · 2025Review
- Curcumin inhibits oxidative stress and autophagy in C17.2 neural stem cell through ERK1/2 signaling pathways.Aging medicine (Milton (N.S.W)) · 2024Article
- Potential nutritional strategies to prevent and reverse sarcopenia in aging process: Role of fish oil-derived ω-3 polyunsaturated fatty acids, wheat oligopeptide and their combined intervention.Journal of advanced research · 2024Article
- Resistance training does not increase myocellular garbage dumps: A pilot study on lipofuscin in skeletal muscle fibers of resistance trained young men.Physiological reports · 2024Article
- Lactate-induced autophagy activation: unraveling the therapeutic impact of high-intensity interval training on insulin resistance in type 2 diabetic rats.Scientific reports · 2024Article
- Lactate activates the mitochondrial electron transport chain independently of its metabolism.Molecular cell · 2023Article
- Insights on the role of L-lactate as a signaling molecule in skin aging.Biogerontology · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of autophagy and lysosomal degradation pathway in the regulation of skeletal muscle metabolism was previously studied. However, underlying molecular mechanisms are poorly understood. L-lactate which is utilized as an energetic substrate by skeletal muscle can also augment genes expression related to metabolism and up-regulate those being responsive to reactive oxygen species (ROS). Since ROS is the most important regulator of autophagy in skeletal muscle, we tested if there is a link between cellular lactate metabolism and autophagy in differentiated C2C12 myotubes and the gastrocnemius muscle of male wistar rats. C2C12 mouse skeletal muscle was exposed to 2, 6, 10, and 20 mM lactate and evaluated for lactate autophagic effects. Lactate dose-dependently increased autophagy and augmented ROS generation in differentiated C2C12 myotubes. The autophagic effect of lactate deterred in N-acetylcysteine presence (NAC, a ROS scavenger) indicated lactate regulates autophagy with ROS participation. Lactate-induced up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) through ROS was required to regulate the autophagy by lactate. Further analysis about ERK1/2 up- and downstream indicated that lactate regulates autophagy through ROS-mediated the activation of ERK1/2/mTOR/p70S6K pathway in skeletal muscle. The in vitro effects of lactate on autophagy also occurred in the gastrocnemius muscle of male Wistar rats. In conclusion, we provided the lactate-associated regulation evidence of autophagy in skeletal muscle by activating ROS-mediated ERK1/2/mTOR/p70S6K pathway. Since the increase in cellular lactate concentration is a hallmark of energy deficiency, the results provide insight into a skeletal muscle mechanism to fulfill its enhanced energy requirement.
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