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

Proc Natl Acad Sci U S A. 2025 Jan 14;122(2):e2407909122. doi: 10.1073/pnas.2407909122. Epub 2025 Jan 9.

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.

Keywords: BH3-only protein; exopher; mitochondria; neuroprotection.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Caenorhabditis elegans* / metabolism
  • Dendrites / metabolism
  • Dendrites / physiology
  • Exocytosis / physiology
  • Mitochondria / metabolism
  • Mitochondrial Dynamics / physiology
  • Neurons* / metabolism
  • Repressor Proteins

Substances

  • Caenorhabditis elegans Proteins
  • EGL-1 protein, C elegans
  • Repressor Proteins