Direkt zum Inhalt
Merck

miR-218 Inhibits Mitochondrial Clearance by Targeting PRKN E3 Ubiquitin Ligase.

International journal of molecular sciences (2020-01-18)
Anthea Di Rita, Teresa Maiorino, Krenare Bruqi, Floriana Volpicelli, Gian Carlo Bellenchi, Flavie Strappazzon
ZUSAMMENFASSUNG

The selective elimination of dysfunctional mitochondria through mitophagy is crucial for preserving mitochondrial quality and cellular homeostasis. The most described mitophagy pathway is regulated by a positive ubiquitylation feedback loop in which the PINK1 (PTEN induced kinase 1) kinase phosphorylates both ubiquitin and the E3 ubiquitin ligase PRKN (Parkin RBR E3 ubiquitin ligase), also known as PARKIN. This event recruits PRKN to the mitochondria, thus amplifying ubiquitylation signal. Here we report that miR-218 targets PRKN and negatively regulates PINK1/PRKN-mediated mitophagy. Overexpression of miR-218 reduces PRKN mRNA levels, thus also reducing protein content and deregulating the E3 ubiquitin ligase action. In fact, following miR-218 overexpression, mitochondria result less ubiquitylated and the autophagy machinery fails to proceed with correct mitochondrial clearance. Since mitophagy defects are associated with various human diseases, these results qualify miR-218 as a promising therapeutic target for human diseases.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Proteasehemmer-Cocktail, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Ziegenserum
Sigma-Aldrich
Natriumorthovanadat, ≥90% (titration)
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
Natriumfluorid, BioXtra, ≥99%