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

Autoři: Tsu-Kung Lin aff001;  Yung-Yee Chang aff001;  Hung-Yu Lin aff003;  Chia-Wei Liou aff001;  Pei-Wen Wang aff004;  Jiin-Haur Chuang aff003;  Shang-Der Chen aff001;  Yao-Chung Chuang aff001;  Sheng-Teng Huang aff005;  Te-Yao Hsu aff006;  Cheng-Huei Peng aff001;  Min-Yu Lan aff001
Působiště autorů: Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff001;  Center for Parkinson’s Disease, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff002;  Department of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff003;  Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff004;  Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan aff005;  Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224173


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.

Klíčová slova:

Central nervous system – Fibroblasts – Mitochondria – Mitochondrial DNA – Mutation – Protein translation – Transfer RNA – Myoclonic epilepsy with ragged red fibers


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2019 Číslo 10