Abstract:
Mitochondrial dynamics is essential for proper neural stem cell differentiation. Previous work in the lab suggests that the mitochondrial inner membrane plays a distinct role in type II neuroblast (NBII) differentiation in Drosophila melanogaster. Though a similar extent of mitochondrial fragmentation is observed when either OPA1, which is responsible for inner membrane fusion and cristae width regulation, or Marf, which is responsible for outer membrane fusion, is depleted in NBII, only OPA1 depletion leads to a striking differentiation defect. Forced fusion of mitochondria by depleting Drp1 in the background of OPA1 depletion rescues this defect by a hypothesized amelioration of cristae morphology in fused mitochondria. The cristae morphology context-dependently modulates the efficiency of the ETC complexes, informing mitochondrial activity. Considering the intimacy of this relationship, we investigated the role of cristae morphology regulatory proteins in NBII differentiation to discover the causal link between the two. Though my work, I was able to demonstrate cristae disruption by hampering ATP synthase dimerisation or L-OPA1 enrichment in NBII causes a significant decrease in the number of differentiated lineage cells. Furthermore, I was able to demonstrate that cristae amelioration is a prerequisite for hyperfusion-mediated rescue of differentiation defect. Furthermore, I was able to demonstrate ROS to be causally linking cristae morphology to NBII differentiation. Additionally, I was able to demonstrate the independent role of ROS in NBII differentiation. Through my work, I have provided strong evidence suggesting cristae morphology to be mediating the interaction between mitochondrial morphology and ETC which coregulate NBII differentiation.
