FIGURE 6.

Model for UBE3B activation in response to calcium signaling/mitochondrial stress. We propose that the E3 ligase UBE3B associates with the mitochondria and that in the absence of stress UBE3B is bound to calmodulin through its N-terminal IQ motif in a calcium-dependent manner. However, in response to mitochondrial stress the intracellular calcium levels increase, thereby activating calmodulin and releasing it from UBE3B. Calmodulin-free UBE3B can now bind to its substrates (potentially damaged mitochondrial proteins) and ubiquitylate substrates for degradation by the UPS.