Mitochondrial uncoupling proteins: redox-metabolic homeostasis and disease pathogenesis

Abstract

Energy, as the main driving force of biological processes, is inextricably linked to life, which represents a continuous flow and utilization of energy. At the center of this process are mitochondria, serving as the primary source of cellular energy. An important point of mitochondrial function is the uncoupling of cellular respiration, a process that influences redox-metabolic homeostasis by modulating both energy expenditure and the production of reactive oxygen species. This is mediated by uncoupling proteins (UCPs), which are involved in the control of ATP synthesis, maintenance of redox homeostasis, thermogenesis, and the regulation of nutrient metabolism. Given their crucial role in redox regulation and energy metabolism, UCPs are under investigation for their possible role in redox-metabolic reprogramming during disease pathogenesis. This review aims to discuss UCPs in relation to the pathophysiology of metabolic diseases such as obesity, diabetes, metabolic dysfunction–associated steatotic liver disease, and cancer, with a focus on their impact on redox homeostasis in order to better understand the potential therapeutic relevance.