Aladin Elkhalil / Biology / Faculty Mentor: Piya Ghose
Programmed cell death (PCD) is a vital cell fate for normal development and homeostasis. Cells that die must be cleared through phagocytosis. Failure to clear cell corpses is implicated in autoimmunity and degenerative disease. Our understanding of PCD in morphologically complex cells is incomplete due to their complex architecture and differing microenvironments between compartments. We present a novel in vivo system to decipher the mechanisms of PCD in complex cells, called Compartmentalized Cell Elimination (CCE). Here, three segments of the C. elegans tail-spike cell and CEM neurons each die in different ways. My work focuses on how CCE is assured during stress. We found mutants for SQSTM1/p62, a scaffold protein that promotes degradation of ubiquitinated proteins by autophagy, have a CCE defect following heat stress. We also found that mutants for SKN-1/Nrf2, a cytoprotective transcription factor that is promoted by SQSTM1/p62, show a similar defect. One transcriptional target of SKN-1/Nrf2 is the lysosomal trafficking gene lyst-1. We find that lyst-1 mutants also have a similar CCE defect, as do mutants for lmp-1/Lamp-1, an important lysosomal gene. Together, our data suggest a novel role for SKN-1/Nrf2 in augmenting lysosomal transport as an adaptive strategy to ensure cell clearance during stress.
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