Leader peptide or pro-segment mutants of renin are misrouted to mitochondria in autosomal dominant tubulointerstitial kidney disease.

ABSTRACT: Autosomal dominant tubulointerstitial kidney disease (ADTKD), a rare genetic disorder characterised by progressive chronic kidney disease, is caused by mutations in different genes, including REN, encoding renin. Renin is a secreted protease composed of three domains: the leader peptide that allows insertion in the endoplasmic reticulum (ER), a pro-segment regulating its activity, and the mature part of the protein. Mutations in mature renin lead to ER retention of the mutant protein and to late-onset disease, whereas mutations in the leader peptide, associated with defective ER translocation, and mutations in the pro-segment, leading to accumulation in the ER-to-Golgi compartment, lead to a more severe, early-onset disease. In this study, we demonstrate a common, unprecedented effect of m

SUBMITTER: Schaeffer C 

PROVIDER: S-EPMC10259838 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature