Golgi disintegration and functional disruption during paraptosis

Paraptosis is a distinct form of programmed cell death characterized by extensive cytoplasmic vacuolation, endoplasmic reticulum (ER) dilation, and mitochondrial swelling. While previous studies have focused primarily on the ER and mitochondria, the involvement of the Golgi apparatus during paraptotic progression remains insufficiently defined. In this study, we identified previously uncharacterized high-density spherical structures, termed paraptosomes, that emerged during paraptosis in human glioblastoma U251MG cells treated with established paraptosis inducers. Further analyses revealed that paraptosome formation coincided with rapid disintegration of the Golgi apparatus, with paraptosomes closely associated with collapsing Golgi structures. Notably, Golgi fragmentation occurred early after paraptosis induction, preceding detectable ER dilation. Functional assessments indicated that Golgi disruption was accompanied by features consistent with Golgi stress responses, including increased expression of Golgi stress-associated markers and impaired secretory capacity. In addition, the ER stress transducers OASIS and ATF6, which normally undergo Golgi-dependent processing and nuclear translocation, failed to be properly processed and instead accumulated within paraptosomes. Collectively, these findings provide an initial structural and cellular-level characterization of paraptosome formation in association with Golgi disintegration and dysfunction, and expand the morphological landscape of paraptosis by identifying Golgi remodeling as an early-associated feature of this non-apoptotic cell death process.