Loss of Prune in Circadian Cells Decreases the Amplitude of the Circadian Locomotor Rhythm in Drosophila .

The circadian system, which has a period of about 24 h, is import for organismal health and fitness. The molecular circadian clock consists of feedback loops involving both transcription and translation, and proper function of the circadian system also requires communication among intracellular organelles. As important hubs for signaling in the cell, mitochondria integrate a variety of signals. Mitochondrial dysfunction and disruption of circadian rhythms are observed in neurodegenerative diseases and during aging. However, how mitochondrial dysfunction influences circadian rhythm is largely unknown. Here, we report that Drosophila prune (pn), which localizes to the mitochondrial matrix, most likely affects the function of certain clock neurons. Deletion of pn in flies caused decreased expression of mitochondrial transcription factor TFAM and reductions in levels of mitochondrial DNA, which resulted in mitochondrial dysfunction. Loss of pn decreased the amplitude of circadian rhythms. In addition, we showed that depletion of mtDNA by overexpression of a mitochondrially targeted restriction enzyme mitoXhoI also decreased the robustness of circadian rhythms. Our work demonstrates that pn is important for mitochondrial function thus involved in the regulation of circadian rhythms.