FIGURE 6.

Deubiquitinating enzymes regulate mitophagy. A: USP30 is anchored in the mitochondrial outer membrane and removes the ubiquitin from Parkin substrates to inhibit mitophagy. B: USP35 counteracts Parkin-mediated mitophagy on healthy mitochondria. USP35 dissociates from depolarized mitochondria to allow mitophagy to proceed. C: Parkin activity is inhibited at baseline via auto-ubiquitination. USP8 preferentially removes ubiquitin conjugates from Parkin. This is required for efficient recruitment of Parkin to depolarized mitochondria.