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Unexpected mitochondrial matrix localization of Parkinson's disease‐related DJ ‐1 mutants but not wild‐type DJ ‐1
Author(s) -
Kojima Waka,
Kujuro Yuki,
Okatsu Kei,
Bruno Queliconi,
Koyano Fumika,
Kimura Mayumi,
Yamano Koji,
Tanaka Keiji,
Matsuda Noriyuki
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12382
Subject(s) - biology , mutant , wild type , mitochondrial matrix , mitochondrion , microbiology and biotechnology , genetics , biochemistry , gene , cytosol , enzyme
DJ ‐1 has been identified as a gene responsible for recessive familial Parkinson's disease (familial Parkinsonism), which is caused by a mutation in the PARK 7 locus. Consistent with the inferred correlation between Parkinson's disease and mitochondrial impairment, mitochondrial localization of DJ ‐1 and its implied role in mitochondrial quality control have been reported. However, the mechanism by which DJ ‐1 affects mitochondrial function remains poorly defined, and the mitochondrial localization of DJ ‐1 is still controversial. Here, we show the mitochondrial matrix localization of various pathogenic and artificial DJ ‐1 mutants by multiple independent experimental approaches including cellular fractionation, proteinase K protection assays, and specific immunocytochemistry. Localization of various DJ ‐1 mutants to the matrix is dependent on the membrane potential and translocase activity in both the outer and the inner membranes. Nevertheless, DJ ‐1 possesses neither an amino‐terminal alpha‐helix nor a predictable matrix‐targeting signal, and a post‐translocation processing‐derived molecular weight change is not observed. In fact, wild‐type DJ ‐1 does not show any evidence of mitochondrial localization at all. Such a mode of matrix localization of DJ ‐1 is difficult to explain by conventional mechanisms and implies a unique matrix import mechanism for DJ ‐1 mutants.