Autophagy is a conserved catabolic process that relies on vacuoles or lysosomes. While autophagosome formation is well characterized, the mechanisms that prevent autophagy-related proteins form being enclosed by the autophagosome and degraded in the vacuole remain unclear in yeast. Here, we show that the SWR1 chromatin remodeling complex plays an essential, noncanonical role in this process. Genome-wide screening identified the SWR1 complex as a critical regulator that prevents the vacuolar delivery of multiple autophagy proteins. This process depends on the structural integrity and ATPase activity of the SWR1 complex. Mechanistically, the SWR1 subunit Rvb1 interacts directly with Atg21, and this interaction is important for SWR1 localization to the phagophore assembly site and efficient protein retrieval. Disruption of the Atg21-Rvb1 interaction results in the vacuolar accumulation of autophagy proteins. These findings uncover an unexpected link between a chromatin remodeling complex and the autophagy machinery, highlighting the Atg21-Rvb1 module as a key regulator of autophagy dynamics in yeast.
Fan et al. (2026) studied this question.