FBS Colloquia No.423Laboratory of Mitochondrial Dynamics

Modified nucleoside export activity and autophagy-dependent degradation of a yeast plasma membrane ABC transporter

Autophagy is an intracellular degradation pathway that is highly conserved from yeast to humans. In this process, intracellular components such as proteins and organelles are sequestered into double-membrane autophagosomes, and subsequently degraded upon fusion with lysosomes (vacuoles in yeast). Recent studies show that RNA is also degraded through autophagy, producing nucleosides and “modified nucleosides” that retain post transcriptional modifications. Because modified nucleosides cannot be reused for de novo nucleotide or nucleic acid synthesis, they are actively exported from the cell. However, the mechanisms underlying this export process remain largely unknown. A genome wide screening in budding yeast performed previously in our laboratory identified a number of nex (nucleoside export) mutants with reduced extracellular modified nucleoside levels. Among these, the first part of this colloquium will focus on Nex1, a plasma membrane ABC transporter implicated in exporting modified nucleosides, and summarize the current findings. Furthermore, in budding yeast, RNA degradation and the extracellular export of modified nucleosides are strongly induced under nitrogen starvation, suggesting that stable plasma membrane localization of Nex1 under starvation is important for its export activity. Interestingly, however, it was revealed that a fraction of Nex1 is degraded under nitrogen starvation. In addition, this degradation appears to occur in an autophagy-dependent manner, which is atypical for plasma membrane proteins. The second part of this colloquium will highlight recent insights into the mechanism of Nex1 degradation and discuss future research directions.