PARL: The mitochondrial rhomboid protease

• Published in: Seminars in cell & developmental biology 2016-12, Vol.60, p.19-28
• Main Authors: Spinazzi, Marco, De Strooper, Bart
• Format: Article
• Language: English
• Subjects: Animals; Cell death; Diabetes Mellitus - enzymology; Humans; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Degradation; Mitochondrial Proteins - metabolism; Parkinson Disease - enzymology; PARL; Protease; Rhomboid; Substrate Specificity
• ISSN: 1084-9521; 1096-3634
• DOI: 10.1016/j.semcdb.2016.07.034

•Mitochondrial rhomboids are evolutionary conserved intramembrane proteases with fundamental, although still incompletely understood, roles in cell homeostasis.•Genetic deletion of mitochondrial rhomboid leads to severe phenotypes in different species.•Knowledge of PARL substrates and physiological function is dynamically evolving, and might uncover differentiations among species.•PARL could play a role in the biology of disease of diabetes and Parkinson’s disease. The rhomboid family comprises evolutionary conserved intramembrane proteases involved in a wide spectrum of biologically relevant activities. A mitochondrion-localized rhomboid, called PARL in mammals, and conserved in yeast and Drosophila as RBD1/PCP1 and rho-7, respectively, plays an indispensable role in cell homeostasis as illustrated by the severe phenotypes caused by its genetic ablation in the various investigated species. Although several substrates of PARL have been proposed to explain these phenotypes, there remains a lot of controversy in this important area of research. We review here the putative functions and substrates of PARL and its orthologues in different species, highlighting areas of uncertainty, and discuss its potential involvement in some prevalent diseases such as type II diabetes and Parkinson’s disease.