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Title: Mitochondrial stress in GABAergic neurons non-cell autonomously regulates organismal health and aging
Abstract Mitochondrial stress within the nervous system can trigger non-cell autonomous responses in peripheral tissues. However, the specific neurons involved and their impact on organismal aging and health have remained incompletely understood. Here, we demonstrate that mitochondrial stress in γ-aminobutyric acid-producing (GABAergic) neurons inCaenorhabditis elegans(C. elegans) is sufficient to significantly alter organismal lifespan, stress tolerance, and reproductive capabilities. This mitochondrial stress also leads to significant changes in mitochondrial mass, energy production, and levels of reactive oxygen species (ROS). DAF-16/FoxO activity is enhanced by GABAergic neuronal mitochondrial stress and mediates the induction of these non-cell-autonomous effects. Moreover, our findings indicate that GABA signaling operates within the same pathway as mitochondrial stress in GABAergic neurons, resulting in non-cell-autonomous alterations in organismal stress tolerance and longevity. In summary, these data suggest the crucial role of GABAergic neurons in detecting mitochondrial stress and orchestrating non-cell-autonomous changes throughout the organism.  more » « less
Award ID(s):
2132286
PAR ID:
10566909
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ;
Publisher / Repository:
bioRxiv
Date Published:
Subject(s) / Keyword(s):
Mitochondria GABAergic neurons GABA aging healthspan reproduction DAF-16/FoxO
Format(s):
Medium: X
Institution:
bioRxiv
Sponsoring Org:
National Science Foundation
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