Circadian rhythms orchestrate a wide array of behavioral and physiological functions, coordinating cellular and organismal processes on an approximately 24-h cycle through an intrinsic timekeeping system. Among the many processes subject to this temporal regulation, mitochondrial function has emerged as a critical and dynamic target of circadian control. Mitochondria, far from being static organelles, undergo continuous morphological remodeling through cycles of fusion and fission, collectively termed mitochondrial dynamics, that are essential for maintaining metabolic homeostasis, energy production, and cellular quality control. Disruptions in circadian rhythmicity, such as those arising from sleep disturbances or irregular feeding patterns, have been associated with impaired glucose tolerance, insulin resistance, and increased risk of metabolic syndrome, diabetes, and cardiovascular disease. Emerging evidence suggests that the circadian clock and mitochondrial dynamics are engaged in a bidirectional interplay, whereby clock-controlled gene expression shapes mitochondrial morphology and function, while mitochondrial metabolic states in turn feedback to influence circadian timing. This review explores the evolutionary origins of mitochondrial rhythmicity, synthesizes current evidence on how the circadian clock regulates mitochondrial dynamics, and examines the physiological and pathological implications of their interconnection. A particular focus is placed on how disruptions in this circadian-mitochondrial axis may contribute to the development of common diseases, including neurodegenerative disorders, metabolic diseases, and cancer, highlighting novel avenues for chronobiologically informed therapeutic strategies.
