Abstract:
Mitochondrial structure is regulated by a dedicated machinery for fusion and fission. Recently mitochondrial architecture regulation is known to be involved in stem cell proliferation and differentiation, and the molecular mechanism underlying the process is not completely understood. In this study, we have used Drosophila neuroblasts as a model system to assess the role of mitochondrial morphology in stem cell development. We found that tissue specific knockdown of mitochondrial fusion proteins Opa1 and Marf showed loss of differentiated population in type II lineage. Interestingly depletion of inner membrane fusion protein Opa1 caused a reduction in both mature intermediate neural precursor (mINP) cells and ganglion mother cell (GMC) population in type II neuroblast lineages. However, depletion of outer membrane fusion protein Marf resulted in a reduction of only GMCs. Loss of differentiation was a consequence of reduced cell proliferation. We found that Notch signaling regulated this fused mitochondrial morphology in type II neuroblasts. Forced outer membrane fusion by depletion of fission protein Drp1 activity led to reversal of differentiation defects seen in notch, opa1 and marf mutants. Similar to opa1, the electron transport chain complex IV and complex V mutants had decreased differentiation. Drp1 depletion reversed the defect in complex IV mutants and not complex V mutants consistent with the crucial role of complex V in cristae stabilization. Our results implicate Notch signaling in regulation of inner membrane in fused mitochondria and show that mitochondrial fusion can compensate for defects in Opa1 and complex IV mutants in neuroblast differentiation.
