How the AMBRA1-RMC1-HUWE1 system controls tagging of mitochondria in specific cell areas

Mitochondrial ubiquitination is linked to the turnover of outer mitochondrial membrane proteins.

• The PINK1-PRKN pathway is known to initiate mitochondrial ubiquitination in response to loss of mitochondrial membrane potential.
• A recruitment platform organized by AMBRA1 facilitates the positioning of HUWE1 at the mitochondria.
• HUWE1 is responsible for the ubiquitination and turnover of key outer mitochondrial membrane proteins such as MFN2, VDAC1, and VDAC2.
• The study raises questions about the selection and potential interactions between different mitochondrial ubiquitination pathways.

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