Insights into the catalytic properties of the mitochondrial rhomboid protease PARL.

ABSTRACT: The rhomboid protease PARL is a critical regulator of mitochondrial homeostasis through its cleavage of substrates such as PINK1, PGAM5, and Smac/Diablo, which have crucial roles in mitochondrial quality control and apoptosis. However, the catalytic properties of PARL, including the effect of lipids on the protease, have never been characterized in vitro. To address this, we isolated human PARL expressed in yeast and used FRET-based kinetic assays to measure proteolytic activity in vitro. We show that PARL activity in detergent is enhanced by cardiolipin, a lipid enriched in the mitochondrial inner membrane. Significantly higher turnover rates were observed for PARL reconstituted in proteoliposomes, with Smac/Diablo being cleaved most rapidly at a rate of 1 min^-1. In contrast, P

SUBMITTER: Lysyk L 

PROVIDER: S-EPMC7966987 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature