EOR-1/PLZF-regulated WAH-1/AIF sequentially promotes early and late stages of non-apoptotic corpse removal.

Programmed cell death (PCD) is a crucial genetically-encoded and evolutionarily-conserved process for development and homeostasis. We previously identified a genetically non-apoptotic, highly ordered, and stereotyped killing program called Compartmentalized Cell Elimination (CCE) in the C. elegans tail-spike epithelial cell (TSC). Here we identify the transcription factor EOR-1/PLZF as promoting CCE. Loss of EOR-1 results in a persisting un-engulfed large soma with enlarged nuclei. We find that EOR-1 and its partners positively regulate the transcription of the Apoptosis Inducing Factor AIF homolog, WAH-1/AIF. We report stereotyped and sequential spatiotemporal dynamics of WAH-1/AIF1 during phagocytosis, with defined roles early and late. Mitochondrial to plasma membrane translocation is required for internalization, and plasma membrane to nuclear translocation for DNA degradation and ultimate corpse resolution. Our study expands our knowledge of PCD by describing a mechanistic contribution of EOR-1/PLZF and functional relevance to specific spatiotemporal contexts for WAH-1/AIF function, and by implying a correlation between DNA degradation with nuclear morphology during cell elimination.
Summary Statement: This work describes the genetic control and cellular dynamics of a factor linked to cancer, metabolic and degenerative disease acting in developmentally dying cells to instruct their own removal.