Interplay of egfr and notch signaling pathways via mitochondrial shape and activity during drosophila development

Abstract

Mitochondrial shape is modulated to regulate their function The regulation of this modulation by cell signalling is not understood well in the field The EGFR and Notch signaling pathways interact with mitochondrial metabolism and morphology during development however the mechanism of interplay is unknown Drosophila melanogaster posterior follicle cells PFCs deficient in mitochondrial fission protein Drp1 showed loss of EGFR signaling driven oocyte axial patterning and Notch signaling mediated PFC differentiation This study elucidates the interaction of these pathways with mitochondrial bioenergetics in the form of electron transport chain ETC activity We show that PFCs deficient for Drp1 have increased mitochondrial membrane potential in addition to aggregated mitochondrial morphology Even though drp1 mutant PFCs show defective oocyte migration phosphorylated ERK dpERK a downstream component of EGFR signaling is elevated in these cells We find that ERK regulates mitochondrial membrane potential at wild type levels in PFCs and increased dpERK in drp1 mutant PFCs is responsible for higher mitochondrial membrane potential Pharmacological inhibition of ETC does not result in change in aggregated mitochondrial morphology in drp1 mutant PFCs or loss of oocyte patterning Notably ETC inhibition activates Notch signaling in wild type ovarioles at an earlier stage and reverses the loss of Notch signaling in drp1 mutant PFCs The positive correlation between EGFR and fragmented mitochondria seems to hold true for Drosophila wing as well Hence EGFR mitochondria might interact in multiple tissues during development Our study thus shows that the EGFR Ras ERK pathway maintains mitochondrial morphology and membrane potential in follicle cells FCs for appropriate activity for oocyte axial patterning and mitochondrial bioenergetics specifically affects Notch mediated differentiation newline newline