Nonapoptotic role of EGL-1 in exopher production and neuronal health in Caenorhabditis elegans

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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 Caenorhabditis elegans, 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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Wu, Z., Cardona, E. A., Cohn, J. A., & Pierce, J. T. (2025). Nonapoptotic role of EGL-1 in exopher production and neuronal health in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 122(2). https://doi.org/10.1073/pnas.2407909122

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