Open AccessMitochondrial dysfunctions in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)
Author(s) -
Tsu-Kung Lin,
YungYee Chang,
HungYu Lin,
ChiaWei Liou,
PeiWen Wang,
JiinHaur Chuang,
ShangDer Chen,
Yao-Chung Chuang,
ShengTeng Huang,
TeYao Hsu,
ChengHuei Peng,
MinYu Lan
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0224173
Subject(s) - mitochondrial dna , biology , mitochondrion , leukodystrophy , dnaja3 , leukoencephalopathy , mitochondrial myopathy , mitochondrial respiratory chain , cellular respiration , microbiology and biotechnology , respiratory chain , genetics , mitochondrial fusion , gene , pathology , medicine , disease
Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.