Exploring the connection between the Mitochondrial DNA and the Circadian Rhythm: Insights into Mitochondrial Biogenesis and its Dynamics

📖 Top 30% JournalOct 1, 2025Molecular biology reports

The link between mitochondrial DNA and the body’s internal clock: understanding mitochondrial growth and changes

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Abstract

Mitochondrial DNA encodes genes essential for mitochondrial function, including oxidative phosphorylation, which generates ATP.

Circadian rhythms, regulated by the suprachiasmatic nucleus, influence various physiological processes on a 24-hour cycle.
Peripheral clocks in tissues connect to the circadian rhythm through mitochondria's role in energy metabolism.
Core clock genes like Bmal1 and Clock are involved in mitochondrial biogenesis and oxidative phosphorylation.
Mitochondrial dysfunction may disrupt circadian rhythms and contribute to metabolic imbalances and disease progression.
There is emerging evidence of a bidirectional relationship between circadian regulation and mitochondrial dynamics.

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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.

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