Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy Depletion.

ABSTRACT: Population genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines. This localization did not depend on the N-terminal signal peptide that mediates APOL1 secretion into the circulation. Additionally, a fraction of these proteins localized to structures surrounding mitocho

SUBMITTER: Granado D 

PROVIDER: S-EPMC5661279 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature