Nonapoptotic role of EGL-1 in exopher production and neuronal health in <i>Caenorhabditis elegans</i>.

Wu, Zheng; Cardona, Eric A; Cohn, Jesse A; Pierce, Jonathan T · Proc Natl Acad Sci U S A · 2025

basic_science · Level V

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Abstract

While traditionally studied for their proapoptotic functions in activating the caspase, research suggests BH3-only proteins also have other roles such as mitochondrial dynamics regulation. Here, we find that EGL-1, the BH3-only protein in <i>Caenorhabditis elegans</i>, promotes the cell-autonomous production of exophers in adult neurons. Exophers are large, micron-scale vesicles that are ejected from the cell and contain cellular components such as mitochondria. EGL-1 facilitates exopher production potentially through regulation of mitochondrial dynamics. Moreover, an endogenous, low level of EGL-1 expression appears to benefit dendritic health. Our findings provide insights into the role of neuronal BH3-only protein in mitochondrial dynamics, downstream exopher production, and ultimately neuronal health.

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