Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity.

There is currently some understanding of the mechanisms that underpin the interactions between circadian rhythmicity and immunity, metabolism and immune response, and circadian rhythmicity and metabolism. In addition, a wealth of studies have led to the conclusion that the commensal microbiota (mainly bacteria) within the intestine contributes to host homeostasis by regulating circadian rhythmicity, metabolism, and the immune system. Experimental studies on how these four biological domains interact with each other have mainly focused on any two of those domains at a time and only occasionally on three. However, a systematic analysis of how these four domains concurrently interact with each other seems to be missing. We have analyzed current evidence that signposts a role for mitochondria as a key hub that supports and integrates activity across all four domains, circadian clocks, metabolic pathways, the intestinal microbiota, and the immune system, coordinating their integration and crosstalk. This work will hopefully provide a new perspective for both hypothesis-building and more systematic experimental approaches.