Sphingosine‐1‐phosphate in mitochondrial function and metabolic diseases

Summary Sphingosine‐1‐phosphate (S1P) is a bioactive sphingolipid metabolite. The past decade has witnessed exponential growth in the field of S1P research, partly attributed to drugs targeting its receptors or kinases. Accumulating evidence indicates that changes in the S1P axis (i.e., S1P production, transport, and receptors) may modify metabolism and eventually mediate metabolic diseases. Dysfunction of the mitochondria on a master monitor of cellular metabolism is considered the leading cause of metabolic diseases, with aberrations typically induced by abnormal biogenesis, respiratory chain complex disorders, reactive oxygen species overproduction, calcium deposition, and mitophagy impairment. Accordingly, we discuss decades of investigation into changes in the S1P axis and how it controls mitochondrial function. Furthermore, we summarize recent scientific advances in disorders associated with the S1P axis and their involvement in the pathogenesis of metabolic diseases in humans, including type 2 diabetes mellitus and cardiovascular disease, from the perspective of mitochondrial function. Finally, we review potential challenges and prospects for S1P axis application to the regulation of mitochondrial function and metabolic diseases; these data may provide theoretical guidance for the treatment of metabolic diseases.