Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy - Archive ouverte HAL
Article Dans Une Revue iScience Année : 2024

Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy

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Centriolar satellites are high-order assemblies, scaffolded by the protein PCM1, that gravitate as particles around the centrosome and play pivotal roles in fundamental cellular processes notably ciliogenesis and autophagy. Despite stringent control mechanisms involving phosphorylation and ubiquitination, the landscape of post-translational modifications shaping these structures remains elusive. Here, we report that necrosulfonamide (NSA), a small molecule known for binding and inactivating the pivotal effector of cell death by necroptosis MLKL, intersects with centriolar satellites, ciliogenesis, and autophagy independently of MLKL. NSA functions as a potent redox cycler and triggers the oxidation and aggregation of PCM1 alongside select partners, while minimally impacting the overall distribution of centriolar satellites. Additionally, NSA-mediated ROS production disrupts ciliogenesis and leads to the accumulation of autophagy markers, partially alleviated by PCM1 deletion. Together, these results identify PCM1 as a redox sensor protein and provide new insights into the interplay between centriolar satellites and autophagy.
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hal-04730345 , version 1 (10-10-2024)

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Clotilde C.N. Renaud, Carolina Alves Nicolau, Clément Maghe, Kilian Trillet, Jane Jardine, et al.. Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy. iScience, 2024, 27 (4), pp.109580. ⟨10.1016/j.isci.2024.109580⟩. ⟨hal-04730345⟩
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