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Glial-derived mitochondrial signals affect neuronal proteostasis and aging. 2023
Raz Bar-Ziv, and
Naibedya Dutta, and
Adam Hruby, and
Edward Sukarto, and
Maxim Averbukh, and
Athena Alcala, and
Hope R Henderson, and
Jenni Durieux, and
Sarah U Tronnes, and
Qazi Ahmad, and
Theodore Bolas, and
Joel Perez, and
Julian G Dishart, and
Matthew Vega, and
Gilberto Garcia, and
Ryo Higuchi-Sanabria, and
Andrew Dillin
Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, The University of California, Berkeley, Berkeley, CA 94720, USA.
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.
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