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Glial-derived mitochondrial signals affect neuronal proteostasis and aging.

Raz Bar-Ziv | Naibedya Dutta | Adam Hruby | Edward Sukarto | Maxim Averbukh | Athena Alcala | Hope R Henderson | Jenni Durieux | Sarah U Tronnes | Qazi Ahmad | Theodore Bolas | Joel Perez | Julian G Dishart | Matthew Vega | Gilberto Garcia | Ryo Higuchi-Sanabria | Andrew Dillin
Science advances | 2023

The nervous system plays a critical role in maintaining whole-organism homeostasis; neurons experiencing mitochondrial stress can coordinate the induction of protective cellular pathways, such as the mitochondrial unfolded protein response (UPRMT), between tissues. However, these studies largely ignored nonneuronal cells of the nervous system. Here, we found that UPRMT activation in four astrocyte-like glial cells in the nematode, Caenorhabditis elegans, can promote protein homeostasis by alleviating protein aggregation in neurons. Unexpectedly, we find that glial cells use small clear vesicles (SCVs) to signal to neurons, which then relay the signal to the periphery using dense-core vesicles (DCVs). This work underlines the importance of glia in establishing and regulating protein homeostasis within the nervous system, which can then affect neuron-mediated effects in organismal homeostasis and longevity.

Pubmed ID: 37831769

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Associated grants

  • Agency: NIEHS NIH HHS, United States
    Id: R01 ES021667
  • Agency: NIA NIH HHS, United States
    Id: T32 AG052374
  • Agency: NHGRI NIH HHS, United States
    Id: P41 HG002223
  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG002223
  • Agency: NIA NIH HHS, United States
    Id: R00 AG065200
  • Agency: NHGRI NIH HHS, United States
    Id: U24 HG002223
  • Agency: NINDS NIH HHS, United States
    Id: T32 NS095939
  • Agency: NIH HHS, United States
    Id: P40 OD010440

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Caenorhabditis Genetics Center (tool)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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