Mitochondrial dysfunctions in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)

Tsu Kung Lin, Yung Yee Chang, Hung Yu Lin, Chia Wei Liou, Pei Wen Wang, Jiin Haur Chuang, Shang Der Chen, Yao Chung Chuang, Sheng Teng Huang, Te Yao Hsu, Cheng Huei Peng, Min Yu Lan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere0224173
JournalPLoS ONE
Volume14
Issue number10
DOIs
StatePublished - 10 2019

Bibliographical note

Publisher Copyright:
© 2019 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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