Publication List English

2017/07/29
New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.

2017/03/09
Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration

2016/07/11
Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish

2016/06/14
Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy

2016/06/07
Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

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.