Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy
Posted on: 19 March 2024 , updated on: 12 January 2025
Preprint posted on 25 January 2024
Article now published in iScience at http://dx.doi.org/10.1016/j.isci.2024.109580
Necrosulfonamide disrupts ciliogenesis and autophagy by inducing PCM1 oxidation and aggregation via ROS production, independent of MLKL.
Selected by Abhishek Poddar
Categories: biochemistry, cell biology, molecular biology
Background:
Centriolar satellites are small, protein assemblies located near centrioles in animal cells. They play a key role in cellular processes such as centriole duplication, ciliogenesis (formation of primary cilium), autophagy and regulation of microtubule dynamics. PCM1 (pericentriolar material 1) is a key component of the centriolar satellites which serves as a molecular scaffold to recruit and organize the structure. This study introduces Necrosulfonamide (NSA), a small molecule known for its role in cell death in crosstalk with centriolar satellites. NSA was found to trigger the oxidation and aggregation of PCM1, independently of MLKL (Mixed Lineage Kinase Domain-Like), a key effector protein in the cell death pathway. NSA also disrupts ciliogenesis and leads to the accumulation of autophagy markers, suggesting that PCM1 acts as a redox sensor protein.
Key findings:
The author discovered that NSA triggers the oxidation and aggregation of PCM1 and other satellite components but does not significantly alter their overall distribution. The authors also found that NSA disrupts ciliogenesis and leads to the accumulation of autophagy markers, and this effect is partially alleviated by deleting PCM1. This discovery provides new insights into the complex interplay between centriolar satellites and autophagy.
What I liked about the research:
The study uncovers NSA’s novel role in PCM1 oxidation and its consequential effects on cellular processes, shedding light on the intricate crosstalk between centriolar satellites, ciliogenesis, and autophagy. It identifies PCM1 as a redox sensor protein and demonstrates the role of NSA in triggering oxidation and aggregation of PCM1. These findings could offer a novel perspective on the regulation of the dynamic relationship between centriolar satellites and autophagy, a key cellular self-cleaning process.
Why this work is promising:
Understanding PCM1’s redox regulation expands knowledge of centriolar satellite functions. NSA’s impact on ciliogenesis and autophagy, independent of MLKL, presents new avenues for research in cell death mechanisms and cellular homeostasis. Understanding the regulation of centriolar satellites and their role in cellular processes is crucial for advancing our knowledge of fundamental cellular biology. This research contributes to our understanding of the post-translational modifications that shape these structures and their impact on ciliogenesis and autophagy. This knowledge could have implications for the development of therapies targeting diseases and syndromes associated with defects in centriolar satellites.
Relevant questions for the authors:
- How does NSA-mediated PCM1 oxidation specifically influence ciliogenesis and autophagy regulation?
- Are there other proteins besides PCM1 in the satellites that may undergo aggregation in response to NSA?
- Could NSA’s impact on cellular processes extend to other PTM pathways or protein networks?
- What are the downstream effects of PCM1 oxidation and aggregation on ciliogenesis and autophagy?
- How does post-translational modifications of PCM1 affect its accumulation?
- How does NSA specifically affect autophagy? Is there an accumulation of autophagosomes?
doi: https://doi.org/10.1242/prelights.39257
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