Mitochondrial respiratory supercomplexes associated with longevity in mammals.

Because of population aging and morbidity expansion, extending healthspan has become a global challenge and it is required to elucidate molecular mechanisms underlying aging and age-related diseases. Mitochondrial dysfunction is a hallmark of aging, characterized by impaired oxidative phosphorylation, increased production of reactive oxygen species (ROS), and metabolic imbalance. Therefore, maintaining mitochondrial homeostasis is essential for healthspan. Mitochondrial respiratory chain complexes organize into higher-order assemblies known as supercomplexes (SCs), which enable to efficient energy or ATP production with repressed ROS generation. Notably, the assembly and stability of these SCs likely decline in aged mammals. In addition, factors such as COX7RP/SCAF1 and mitochondrial lipid cardiolipin have emerged as key regulators of SC assembly. In this review, we summarize the molecular assembly, physiological roles, and longevity implications of SC in healthy mammals. We further discuss emerging evidence supporting SC modulation as a potential strategy for promoting healthy aging.