Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy

Abstract

(PCM1) protein, that gravitate as particles around the centrosome. Centriolar satellites have been linked to key cellular processes including the formation of primary cilia and GABARAP-mediated autophagy. However, to date, there is no pharmacological inhibitor of centriolar satellites. Here, we report that necrosulfonamide (NSA), a compound previously shown to target the cell death effector MLKL, induced non-degradative ubiquitination of PCM1. This also caused a defect in ciliogenesis and an accumulation of autophagy markers such as P62 and GABARAPL1, although the overall architecture and distribution of centriolar satellites were maintained. We further found that the depletion of PCM1 lessened the impact of NSA on autophagy. Altogether, NSA may be a valuable tool to study centriolar satellites and provide further insights into their interplay with autophagy.