Fig. 7: Current hypothetical model for Complex I-induced protein turnover of MCU.
Top, under physiological conditions, MCU interacts with Complex I and is oxidized by the mild ROS leak produced by Complex I. Such oxidized MCU becomes damaged and degraded by LONP1 or other quality-control proteases, leaving Complex I available to interact with additional channels. We term this process Complex I-induced protein turnover (CLIPT). Bottom, when Complex I becomes impaired or misassembled, it produces excessive ROS and self-inactivates. Such dysfunctional Complex I can no longer interact with MCU, nor damage it with basal ROS leak, and is cleared by housekeeping proteases CLPP and LONP1. Thus, functional MCU levels build up, and additional Ca2+ influx through these channels maintains energetic homeostasis.
