Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans

种系蛋白质稳态对线粒体的系统性调节可防止秀丽隐杆线虫体细胞中的蛋白质聚集

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作者:Giuseppe Calculli, Hyun Ju Lee, Koning Shen, Uyen Pham, Marija Herholz, Aleksandra Trifunovic, Andrew Dillin, David Vilchez

Abstract

Protein aggregation causes intracellular changes in neurons, which elicit signals to modulate proteostasis in the periphery. Beyond the nervous system, a fundamental question is whether other organs also communicate their proteostasis status to distal tissues. Here, we examine whether proteostasis of the germ line influences somatic tissues. To this end, we induce aggregation of germline-specific PGL-1 protein in germline stem cells of Caenorhabditis elegans Besides altering the intracellular mitochondrial network of germline cells, PGL-1 aggregation also reduces the mitochondrial content of somatic tissues through long-range Wnt signaling pathway. This process induces the unfolded protein response of the mitochondria in the soma, promoting somatic mitochondrial fragmentation and aggregation of proteins linked with neurodegenerative diseases such as Huntington's and amyotrophic lateral sclerosis. Thus, the proteostasis status of germline stem cells coordinates mitochondrial networks and protein aggregation through the organism.

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