Regulation of Mitochondrial Quality Control Mechanisms in the Kidney by the Pharmacological Activation of the 5-Hydroxytryptamine 1F Receptor

Abstract

Serotonin, while conventionally known as a neurotransmitter in the central nervous system, has recently gained attention for its role in the kidney. Serotonin is not only synthesized in the kidney, but also regulates glomerular function, vascular resistance, and mitochondrial homeostasis. Mitochondrial dysfunction can result from injury or disease development and is characterized by oxidative stress, decreased respiratory capacity, ATP depletion, membrane integrity loss, and cytochrome c release. This review focuses on the role of serotonin and its receptors in mitochondrial function and kidney diseases, namely acute kidney injury, chronic kidney disease, and diabetic kidney disease, all of which are characterized by mitochondrial dysfunction and none of which have approved pharmacological treatments. Evidence indicates that activation of certain serotonin receptors can stimulate mitochondrial biogenesis (MB) and restore mitochondrial homeostasis, resulting in improved renal function. Serotonin receptor agonists that induce MB are therefore of interest as potential therapeutic strategies for renal injury and disease.