Mitochondrial DNA (mtDNA), inherited exclusively from the mother, encodes genes essential for mitochondrial function, including oxidative phosphorylation (OXPHOS), which generates ATP, the cell's primary energy currency. Circadian rhythm is a crucial biological system that refers to the innate biological clock, whose core is in the suprachiasmatic nucleus (SCN) of the brain. This nucleus regulates various physiological processes, such as sleep-wake cycles, hormone secretion, cellular repair, energy homeostasis, and metabolism, on a roughly 24-hour cycle. Peripheral clocks exist in various tissues, including cells sensitive to external stimuli, and are linked to the circadian rhythm due to mitochondria's role in cellular energy metabolism. Core clock genes like Bmal1 and Clock influence mitochondrial biogenesis, oxidative phosphorylation, and mitophagy, while mitochondrial dysfunction disrupts circadian rhythms, leading to metabolic imbalance and disease progression. Emerging research suggests a bidirectional connection between circadian regulation and mitochondrial dynamics. This review focuses on the complex interplay between the circadian rhythm and mitochondrial processes, as regulated by various cellular proteins, transcription factors, ions, receptors, channels, and the mitochondrial genetic machinery, to understand the harmonious coordination between energy metabolism and timing mechanisms needed to optimize cellular processes and maintain physiological balance. The study of this relationship provides new insights into aging, neurodegenerative disorders, and metabolic diseases, potentially guiding future interventions focusing on chronotherapy and mitochondrial targeting.
