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铁蛋白重链可保护发育中的翅膀免受活性氧和铁死亡的侵害。

Ferritin heavy chain protects the developing wing from reactive oxygen species and ferroptosis.

机构信息

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.

Electron Microscopy Facility, University of Lausanne, Lausanne, Switzerland.

出版信息

PLoS Genet. 2019 Sep 30;15(9):e1008396. doi: 10.1371/journal.pgen.1008396. eCollection 2019 Sep.

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.

摘要

信号通路与代谢之间的相互作用对于组织生长至关重要。然而,这方面的了解仍很有限。在这里,我们研究了调节铁代谢对果蝇 imaginal 盘生长的影响。我们发现,减少幼虫翅膀盘中铁蛋白重链的水平会导致严重的生长缺陷,而轻链耗尽只会导致轻微的缺陷。重链的突变细胞克隆缺乏与 Minute 突变细胞竞争的能力。ROS 在铁蛋白水平降低的翅膀盘中积累,导致严重的线粒体缺陷和铁死亡。阻止 ROS 积累可缓解部分生长缺陷。我们提出,hippo 突变细胞中 ferritin 的高表达可能有助于防止 ROS 积累。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f365/6786644/8d63a96c929d/pgen.1008396.g001.jpg

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