Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics

Yuki Miyamoto, Takahiro Eguchi, Kazuko Kawahara, Nanami Hasegawa, Kazuaki Nakamura, Megumi Tago, Akito Tanoue, Hiroomi Tamura, Junji Yamauchi

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Myelin-forming glial cells undergo dynamic morphological changes in order to produce mature myelin sheaths with multiple layers. In the central nervous system (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but their related disorders lead not only to dismyelination and repeated demyelination but also to severe neuropathies. Hereditary hypomyelinating leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes and are often caused by missense mutations of the respective responsible genes. Despite increasing identification of gene mutations through advanced nucleotide sequencing technology, studies on the relationships between gene mutations and their effects on cellular and subcellular aberrance have not followed at the same rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly) mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length morphologies and increases the numbers of mitochondria due to their aberrant fission and fusion cycles. In experiments using a fluorescent dye probe, this mutation decreases the mitochondrial membrane potential. Also, mitochondria accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This study constitutes a first finding concerning the relationship between disease-associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the relationship between another disease-associated HSPD1 mutation (MitCHAP-60 disease) and aberrant mitochondrial dynamics.

Original languageEnglish
Pages (from-to)275-281
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume462
Issue number3
DOIs
Publication statusPublished - 2015 Jun 3

Fingerprint

Mitochondrial Dynamics
Missense Mutation
Myelin Sheath
Oligodendroglia
Mutation
Mitochondria
Genes
Neurology
Fluorescent Dyes
Chaperonin 60
Mitochondrial Membrane Potential
Demyelinating Diseases
Fusion reactions
Nucleotides
Neuroglia
Nervous System
Axons
Membranes
Homeostasis
Central Nervous System

Keywords

  • Dynamics
  • Fission and fusion cycle
  • HLD4
  • HSPD1
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics. / Miyamoto, Yuki; Eguchi, Takahiro; Kawahara, Kazuko; Hasegawa, Nanami; Nakamura, Kazuaki; Tago, Megumi; Tanoue, Akito; Tamura, Hiroomi; Yamauchi, Junji.

In: Biochemical and Biophysical Research Communications, Vol. 462, No. 3, 03.06.2015, p. 275-281.

Research output: Contribution to journalArticle

Miyamoto, Yuki ; Eguchi, Takahiro ; Kawahara, Kazuko ; Hasegawa, Nanami ; Nakamura, Kazuaki ; Tago, Megumi ; Tanoue, Akito ; Tamura, Hiroomi ; Yamauchi, Junji. / Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 462, No. 3. pp. 275-281.
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