4.8 Article

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

Journal

SCIENCE ADVANCES
Volume 7, Issue 26, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abg3012

Keywords

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Funding

  1. European Research Council (ERC) [677427 StemProteostasis]
  2. Center for Molecular Medicine Cologne (C16)
  3. Deutsche Forschungsgemeinschaft (DFG) [VI742/4-1]
  4. Deutsche Forschungsgemeinschaft (DFG) (Germany's Excellence Strategy-CECAD) [EXC 2030-390661388]

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Research shows that the proteostasis of germline stem cells can influence the entire organism, including somatic tissues, by regulating mitochondrial networks and protein aggregation, thereby affecting biological processes in distal tissues.
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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