ERK regulates mitochondrial membrane potential in fission deficient Drosophila follicle cells during differentiation

Developmental biology

Darshika Tomer^1¹  Rohan Chippalkatti^1² 

[1]Biology, Indian Institute of Science Education and Research, Homi Bhabha Road, Pashan, Pune 411008, India^1

[2]Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA^2

关键词: PFC;    Posterior Follicle Cells;    EGFR;    Epidermal Growth Factor Receptor;    NICD;    Notch Intra-Cellular Domain;    ROS;    Reactive Oxygen Species;    ETC;    Electron Transport Chain;    Ψm;    Mitochondrial Membrane Potential;    Mitochondria;    Signaling;    Drosophila;    ERK;    Notch;   

DOI  :  10.1016/j.ydbio.2017.11.009

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

Mitochondrial morphology regulatory proteins interact with signaling pathways involved in differentiation. In Drosophila oogenesis, EGFR signaling regulates mitochondrial fragmentation in posterior follicle cells (PFCs). EGFR driven oocyte patterning and Notch signaling mediated differentiation are abrogated when PFCs are deficient for the mitochondrial fission protein Drp1. It is not known whether fused mitochondrial morphology in drp1 mutant PFCs exerts its effects on these signaling pathways through a change in mitochondrial electron transport chain (ETC) activity. In this study we show that aggregated mitochondria in drp1 mutant PFCs have increased mitochondrial membrane potential. We perform experiments to assess the signaling pathway regulating mitochondrial membrane potential and how this impacts follicle cell differentiation. We find that drp1 mutant PFCs show increase in phosphorylated ERK (dpERK) formed downstream of EGFR signaling. ERK regulates high mitochondrial membrane potential in drp1 mutant PFCs. PFCs depleted of ERK and drp1 are able to undergo Notch mediated differentiation. Notably mitochondrial membrane potential decrease via ETC inhibition activates Notch signaling at an earlier stage in wild type and suppresses the Notch signaling defect in drp1 mutant PFCs. Thus, this study shows that the EGFR pathway maintains mitochondrial morphology and mitochondrial membrane potential in follicle cells for its functioning and decrease in mitochondrial membrane potential is needed for Notch mediated differentiation.

【 授权许可】

CC BY