Vps13 is required for timely removal of nurse cell corpses.

Programmed cell death and consecutive removal of cellular remnants is essential for development. During late stages of Drosophila melanogaster oogenesis, the small somatic follicle cells that surround the large nurse cells promote non-apoptotic nurse cell death, subsequently engulf them, and contribute to the timely removal of nurse cell corpses. Here, we identify a role for Vps13 in the timely removal of nurse cell corpses downstream of developmental programmed cell death. Vps13 is an evolutionarily conserved peripheral membrane protein associated with membrane contact sites and lipid transfer. It is expressed in late nurse cells, and persistent nurse cell remnants are observed when Vps13 is depleted from nurse cells but not from follicle cells. Microscopic analysis revealed enrichment of Vps13 in close proximity to the plasma membrane and the endoplasmic reticulum in nurse cells undergoing degradation. Ultrastructural analysis uncovered the presence of an underlying Vps13-dependent membranous structure in close association with the plasma membrane. The newly identified structure and function suggests the presence of a Vps13-dependent process required for complete degradation of bulky remnants of dying cells.

SK channel activation is neuroprotective in conditions of enhanced ER-mitochondrial coupling.

Alterations in the strength and interface area of contact sites between the endoplasmic reticulum (ER) and mitochondria contribute to calcium (Ca2+) dysregulation and neuronal cell death, and have been implicated in the pathology of several neurodegenerative diseases. Weakening this physical linkage may reduce Ca2+ uptake into mitochondria, while fortifying these organelle contact sites may promote mitochondrial Ca2+ overload and cell death. Small conductance Ca2+-activated K+ (SK) channels regulate mitochondrial respiration, and their activation attenuates mitochondrial damage in paradigms of oxidative stress. In the present study, we enhanced ER-mitochondrial coupling and investigated the impact of SK channels on survival of neuronal HT22 cells in conditions of oxidative stress. Using genetically encoded linkers, we show that mitochondrial respiration and the vulnerability of neuronal cells to oxidative stress was inversely linked to the strength of ER-mitochondrial contact points and the increase in mitochondrial Ca2+ uptake. Pharmacological activation of SK channels provided protection against glutamate-induced cell death and also in conditions of increased ER-mitochondrial coupling. Together, this study revealed that SK channel activation provided persistent neuroprotection in the paradigm of glutamate-induced oxytosis even in conditions where an increase in ER-mitochondrial coupling potentiated mitochondrial Ca2+ influx and impaired mitochondrial bioenergetics.