Succinate as a metabolic-signaling dual-function hub in skeletal muscle: linking exercise adaptation to myopathic dysfunction.

Skeletal muscle plasticity is shaped by mechanical loading, metabolic flux, and intercellular signaling. Beyond its canonical role as a tricarboxylic acid (TCA) cycle intermediate, succinate is increasingly viewed as a potential extracellular signaling metabolite that may link mitochondrial metabolism to tissue remodeling. However, whether succinate acts as a causal mediator rather than a correlate of metabolic stress remains incompletely defined. In this hypothesis-driven narrative review, we propose the Succinate Dual-Function Hub framework, in which succinate is considered a context-dependent metabolic signal whose effects may depend on kinetics, concentration, compartmentalization, receptor availability, transport capacity, and co-emergent exercise signals. Current evidence suggests that high-intensity contraction can induce transient succinate accumulation and release, which may contribute to mitochondrial remodeling, vascular or niche-related signaling, immune regulation, and satellite cell responses through SUCNR1-dependent and SUCNR1-independent mechanisms. In contrast, sustained succinate elevation associated with mitochondrial dysfunction or metabolic disease has been linked to inflammatory, epigenetic, and oxidative stress-related programs. This adaptive-maladaptive distinction should be viewed as a testable organizing model rather than an established causal rule. We discuss key evidence gaps and the preliminary translational potential of the succinate-SUCNR1 axis as a candidate biomarker or research target for myopathic conditions.