SLC25 in intestinal inflammation: mechanisms, pathological roles, and therapeutic implications.

Inflammatory bowel diseases (IBD) represent a spectrum of chronic gastrointestinal disorders fueled by a complex multifactorial interplay, where mitochondrial dysfunction has emerged as a critical contributor. The SLC25 family of mitochondrial transporters mediates the exchange of essential metabolites across the mitochondrial inner membrane, serving as pivotal regulators of cellular energy homeostasis in both the intestinal epithelium and immune cells. Accumulating evidence indicates that dysregulation of SLC25-dependent metabolic transport disrupts the crosstalk between cellular metabolism and immune signaling, driving chronic intestinal inflammation. This review comprehensively examines the pathological roles of SLC25 proteins across three interconnected dimensions: epithelial barrier disruption, immune dysregulation, and host-microbiota metabolic crosstalk. Specifically, we synthesize current findings on how altered SLC25 function compromises the intestinal barrier via oxidative stress and energy deficits, skews immune cell polarization toward pro-inflammatory states, and perpetuates a vicious cycle of microbial dysbiosis. Ultimately, this review provides a comprehensive theoretical basis for the central role of SLC25-mediated metabolic reprogramming in IBD pathogenesis, and establishes a critical mechanistic foundation for the development of novel metabolism-targeted therapeutics and diagnostic biomarkers.