Abstract
The interplay between signalling pathways and metabolism is crucial for tissue growth. Yet, it remains poorly understood. Here, we studied the consequences of modulating iron metabolism on the growth of Drosophila imaginal discs. We find that reducing the levels of the ferritin heavy chain in the larval wing discs leads to drastic growth defects, whereas light chain depletion causes only minor defects. Mutant cell clones for the heavy chain lack the ability to compete against Minute mutant cells. Reactive oxygen species (ROS) accumulate in wing discs with reduced heavy chain levels, causing severe mitochondrial defects and ferroptosis. Preventing ROS accumulation alleviates some of the growth defects. We propose that the increased expression of ferritin in hippo mutant cells may protect against ROS accumulation.
Highlights
Iron is indispensable for the well-being of cells, from prokaryotes to eukaryotes
As multiple Ferritin 1 Heavy Chain Homolog (Fer1HCH) RNAi lines led to growth defects and modified Hippo phenotypes, we decided that the potential role of Fer1HCH in growth control was worthy of further study
We studied the function of the two ferritin subunits in growth control during Drosophila larval disc development, a well-established model system for epithelial morphogenesis and tumorigenesis
Summary
Iron is indispensable for the well-being of cells, from prokaryotes to eukaryotes. Many key enzymes involved in ATP production, photosynthesis, and DNA biosynthesis require iron-sulphur clusters to function [1, 2]. Ferrous iron (Fe2+) is readily converted to the ferric iron (Fe3+) under aerobic conditions or via the Fenton reaction. The latter reaction generates reactive oxygen species, which damage biological macromolecules. The function of ferritin has been studied in different contexts and the emerging view is that its main role is to sequester iron and keep it in a non-toxic form [5]. This potentially protects the cells from apoptosis and gives them a proliferative advantage.
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