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The endosymbiotic cellular organelles, mitochondria, are central players in various cellular processes beyond their
classical role in energy metabolism. Mitochondrial structure–function is dynamic, which is modulated by fission and fusion events
brought about by specific proteins between individual mitochondria. Such dynamic plasticity of mitochondria is critical for
maintaining stem cell properties. It remains to be understood how stem cell regulatory signals are integrated by mitochondria
to reshape cellular metabolism. We and others had previously identified a state of stem cells that are primed by mitochondria.
Particularly, fine-tuned repression of mitochondrial fission, driven by the Dynamin Related Protein 1(Drp1), elevates self-renewal
of tested adult stem cells by ~10 folds, and makes them prone to carcinogenesis. More recently, we found such mitochondrial
priming in Drosophila ovarian germline stem cells (GSCs) markedly boosts female reproductive ability (egg laying). Lineage tracing
with Drp1 hypomorphic mutants and RNAi experiments revealed that tuned Drp1 repression boosts both self-
renewal/proliferation and differentiation of GSCs and only self-renewal/proliferation of the somatic stem cells of the ovary.
Interestingly, GSC priming related tuned repression of Drp1 leads to enhanced recruitment of Drp1 to mitochondria. Strikingly,
Drp1-dependent stem cell priming is observed only under protein supplementation or high-sugar diet, and is strictly under the
influence of alternating light–dark cycle. Our data suggests that the classically characterized photoreceptor, Cryptochrome,
integrates light and dietary cues with Drp1 driven mitochondrial fission, absence of which prevents GSC priming. Ongoing studies
aim to examine if such integration involves Drp1 driven modulation of mitochondrial utilization of carbon sources in protein and
sugar rich dietary conditions. Together, these findings support Cryptochrome-mediated Drp1 repression as a plausible
mechanistic link between circadian and metabolic regulation of stem cell fate. |