Nuclear degradation is a major event during programmed cell death (PCD). The breakdown of nuclear components has been well characterized during apoptosis, one form of PCD. Many nonapoptotic forms of PCD have been identified, but our understanding of nuclear degradation during those events is limited. Here, we take advantage of Drosophila oogenesis to investigate nuclear degeneration during stress-induced apoptotic and developmental nonapoptotic cell death in the same cell type in vivo. We find that nuclear Lamin, a caspase substrate, dissociates from the nucleus as an early event during apoptosis, but remains associated with nuclei during nonapoptotic cell death. Lamin reveals a series of changes in nuclear architecture during nonapoptotic death, including nuclear crenellations and involutions. Stretch follicle cells contribute to these architecture changes, and phagocytic and lysosome-associated machinery in stretch follicle cells promote Lamin degradation. More specifically, we find that the lysosomal cathepsin CP1 facilitates Lamin degradation.
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We thank the members of our lab for valuable discussions and comments, especially Anoush Calikyan and Jeanne Peterson for assistance. We thank Todd Blute for microscopy help, Katia Oleinik for helping AY with R, and Nicholas Ray for help with Lamin degradation analyses. The Lamin ADL84.12 antibody developed by Paul A. Fisher was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biology, Iowa City, IA 52242. We thank our funding sources: NIH Grants R01 GM060574 and R35 GM127338 to KM, NIH F31 GM115177 to AAM, and the AAUW Dissertation Fellowship to AY.
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Yalonetskaya, A., Mondragon, A.A., Hintze, Z.J. et al. Nuclear degradation dynamics in a nonapoptotic programmed cell death. Cell Death Differ 27, 711–724 (2020). https://doi.org/10.1038/s41418-019-0382-x