Publication List English

2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis

2021/08/19
Patient-Derived Cancer Xenograft Zebrafish Model (PDXZ) for Drug Discovery Screening and Personalized Medicine

2021/07/09
Quality Control Protocol for Zebrafish Developmental Toxicity Studies

2020/10/13
Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish

2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis

tS-nitrosylation regulates mitochondrial quality control via activation of parkin.

                     
2013/07/15

Parkin, a ubiquitin E3 ligase of the ring between ring fingers family, has been implicated in mitochondrial quality control. A series of recent reports have suggested that the recruitment of parkin is regulated by phosphorylation. However, the molecular mechanism that activates parkin to induce mitochondrial degradation is not well understood. Here, and in contrast to previous reports that S-nitrosylation of parkin is exclusively inhibitory, we identify a previously unrecognized site of S-nitrosylation in parkin (Cys323) that induces mitochondrial degradation. We demonstrate that endogenous S-nitrosylation of parkin is in fact responsible for activation of its E3 ligase activity to induce aggregation and degradation. We further demonstrate that mitochondrial uncoupling agents result in denitrosylation of parkin, and that prevention of denitrosylation restores mitochondrial degradation. Our data indicates that NO both positive effects on mitochondrial quality control, and suggest that targeted S-nitrosylation could provide a novel therapeutic strategy against Parkinson's disease.

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Scientific Reports

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S-nitrosylation regulates mitochondrial quality control via activation of parkin.