Interaction of light-dark and dietary cues prime Drosophila ovarian stem cell properties by precisely tuning Drp1 recruitment and organization on mitochondria

The quiescent adult stem cells are activated to maintain tissue integrity. Mitochondria have emerged as critical regulators of stem/progenitor cells. Scattered literature suggests existence of a high-potency stemness state with characteristic mitochondrial structure-function properties that may ‘prime’ stem cell activation. Precise tuning of mitochondrial structure by the mitochondrial fission protein, Drp1, can prime a stem cell state for neoplasticity in vitro. However, the in vivo significance and regulation of such a proposed ‘primed’ stemness state remains elusive. We use quantitative genetic and cell biological approaches to demonstrate that light-dark cycling driven precise tuning of Drp1 primes the Drosophila ovarian germline stem cell (GSC) response to protein-rich dietary supplement towards stimulating egg production. This can be reversed by repressing mitochondrial fusion protein, Opa1, and is disrupted in the absence of functional Cry protein that maintains light-dark rhythm. Mechanistically, this is achieved by light or dark allowing protein-rich supplements to stimulate distinct characteristic recruitment and organization of Drp1 on mitochondria in GSC subpopulations. Screening of essential amino acids reveals the importance of interaction between Threonine supplementation, Cry, Drp1 and Opa1 in such priming of the GSCs and egg production. The priming of the ovarian follicle stem cells happens at a different tuned level of Drp1. Such Drp1-tuning driven priming of Drosophila ovarian stem cells reverses the inhibitory impact of diabetes-like condition on egg development in the presence of protein-rich supplement. Thus, our study revealing the paradigm of adult stem cell regulation by integration of light-dark and dietary cues via precise mitochondrial modulation, is significant in regenerative health and degenerative diseases.