English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Significance VDAC1 transports ions and small molecules at the mitochondrial outer membrane. In this study, we discover that Parkin, a frequently mutated Parkinson disease protein, ubiquitinates VDAC1 in two different manners, poly- and monoubiquitination. Interestingly, VDAC1 defective in polyubiquitination hinders Parkin-mediated mitophagy, but VDAC1 defective in monoubiquitination induces apoptosis. When VDAC1 deficient with monoubiquitination is expressed in mammalian cells and fruit fly, we observe increased mitochondrial calcium influx and apoptosis and typical in vivo phenotypes related to Parkinson disease, such as defective locomotive activity and loss of dopaminergic neurons. These results suggest that the dual regulation of mitophagy and apoptosis by Parkin via VDAC1 poly- and monoubiquitination is highly critical in protecting cells from the pathogenesis of Parkinson disease.

Decision between mitophagy and apoptosis by Parkin via VDAC1 ubiquitination