LAUSR

Significance A hypothesis for the paradoxical evolution of programmed cell death posits that suicide mechanisms were co-opted from processes that were originally pro-survival. Here we show that meiotically programmed mitochondrial release of the Endonuclease G (EndoG) homolog Nuc1 occurs during sporulation in budding yeast. While EndoG release is implicated in animal cell apoptotic death, we find that Nuc1 release is pro-survival, protecting spores from the detrimental consequences of unrestrained viral expression. The programmed release of apoptogenic proteins from mitochondria is a core event of apoptosis, although ancestral roles of this phenomenon are not known. In mammals, one such apoptogenic protein is Endonuclease G (EndoG), a conserved mitochondrial nuclease that fragments the DNA of dying cells. In this work, we show that budding yeast executes meiotically programmed mitochondrial release of an EndoG homolog, Nuc1, during sporulation. In contrast to EndoG’s ostensible pro-death function during apoptosis, Nuc1 mitochondrial release is pro-survival, attenuating the cytosolic L-A and Killer double-stranded RNA mycoviruses and protecting meiotic progeny from the catastrophic consequences of their derepression. The protective viral attenuation role of this pathway illuminates a primordial role for mitochondrial release of EndoG, and perhaps of apoptosis itself.