Abstract
Mitochondrial Calcium Uniporter serves as the major portal for calcium influx into the matrix. It is a highly regulated ion channel complex composed of the pore forming subunit MCU and multiple regulatory subunits, among which the Essential MCU REgulator (EMRE) is necessary for the calcium conducting function of MCU. The goal of this work is to understand how cells regulate EMRE expression level. Using a cycloheximide chase assay, I found that MCU protects EMRE from rapid proteolysis by the mitochondrial m-AAA (ATPases Associated with diverse cellular Activities) protease. Experiments show that such protection requires interactions between the two proteins’ transmembrane helices (TMHs). Then I use EMRE homologues and chimeras to show that the rate-limiting step for EMRE degradation occurs after initial protease binding to the EMRE’s N-terminus. This work revealed a post-translational mechanism by which balanced expression of uniporter subunits is achieved, a condition that might be crucial for proper assembly of the uniporter complex.