Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy

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 ubiquitin...

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Published iniScience Vol. 27; no. 4; p. 109580
Main Authors Renaud, Clotilde C.N., Nicolau, Carolina Alves, Maghe, Clément, Trillet, Kilian, Jardine, Jane, Escot, Sophie, David, Nicolas, Gavard, Julie, Bidère, Nicolas
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 19.04.2024
Elsevier
Subjects
Biological sciences
Life Sciences
Molecular biology
Molecular interaction
Molecular biology
Molecular interaction
Biological sciences
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Summary: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. [Display omitted] •Necrosulfonamide (NSA) functions as a redox cycler independently of MLKL•PCM1 and several centriolar satellite components are redox sensor proteins•NSA-mediated ROS production prevents the formation of primary cilia•NSA interferes with autophagy partly via PCM1 Biological sciences; Molecular biology; Molecular interaction
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These authors contributed equally
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109580