Ubiquilins Chaperone and Triage Mitochondrial Membrane Proteins for Degradation

• DOI: 10.1016/j.molcel.2016.05.020
• Publication Date: 2016-06-25T07:37:23Z
• Authors: Eisuke Itakura; Eszter Zavodszky; Sichen Shao; Matthew L. Wohlever; Robert J. Keenan; Ramanujan S. Hegde
• Keywords: Chaperone (clinical); Proteostasis

We investigated how mitochondrial membrane proteins remain soluble in the cytosol until their delivery to mitochondria or degradation at proteasome. show that Ubiquilin family bind transmembrane domains prevent aggregation and temporarily allow opportunities for targeting. Over time, Ubiquilins recruit an E3 ligase ubiquitinate bound clients. The attached ubiquitin engages Ubiquilin's UBA domain, normally intramolecular UBL stabilizes Ubiquilin-client complex. This conformational change precludes additional chances targeting client, while simultaneously freeing domain Loss of by genetic ablation sequestration polyglutamine aggregates leads accumulation non-inserted protein precursors. These findings define as a chaperones cytosolically exposed explain they use triage clients via coordinated intra- intermolecular interactions.