Figure 7. Proposed model of stress-induced proton transport mechanism of neuronal UCPs.

Under oxidative stress, lipolysis can be activated through enzymes such as mitochondrial phospholipase A2. The lipolysis of mitochondrial phospholipid releases free FAs and their oxidized derivatives (e.g., FAOOH), which can directly interact with UCPs and activate the proton transport. Each neuronal UCP might possess a specific FA-binding site. The FA-binding sites of neuronal UCPs could have an optimal binding affinity for FAs that are available in specific expression tissues. The proton transport mediated by neuronal UCPs can help reduce the membrane potential across the IMM and consequently lower ROS production.