Neuron-specific knockdown of solute carrier protein SLC25A46a induces locomotive defects, an abnormal neuron terminal morphology, learning disability, and shortened lifespan

Ali, Saheb; Suda, Kojiro; Kowada, Ryosuke; Ueoka, Ibuki; Yoshida, Hideki; Yamaguchi, Masamitsu

doi:10.1016/j.ibror.2020.02.001

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…The diverse symptoms of diseases caused by mutations in SLC25A46 may be related to the dysregulation of epigenetic mechanisms. There are two homologues of human SLC25A46 in Drosophila, designated as dSLC25A46a ( CG8931 ) [ 159 ] and dSLC25A46b ( CG5755 ) [ 160 ]. Drosophila models targeting dSLC25A46a or dSLC25A46b exhibited similar phenotypes such as locomotive defects and aberrant morphology of synapses at the NMJ [ 159 , 160 ].…”

Section: Epigenetic Regulation Of Cmtmentioning

confidence: 99%

“…There are two homologues of human SLC25A46 in Drosophila, designated as dSLC25A46a ( CG8931 ) [ 159 ] and dSLC25A46b ( CG5755 ) [ 160 ]. Drosophila models targeting dSLC25A46a or dSLC25A46b exhibited similar phenotypes such as locomotive defects and aberrant morphology of synapses at the NMJ [ 159 , 160 ]. Gene Expression Omnibus (GEO) analysis revealed that HDAC1 is associated with several SLC25A46 genomic regions in human cultured CD4-positive cells, and this association was further evaluated using the Drosophila models [ 161 ].…”

Section: Epigenetic Regulation Of Cmtmentioning

confidence: 99%

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Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models

Yamaguchi

Omori

Asada

et al. 2021

IJMS

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Amyotrophic lateral sclerosis (ALS) is the third most common neurodegenerative disorder and is sometimes associated with frontotemporal dementia. Charcot–Marie–Tooth disease (CMT) is one of the most commonly inherited peripheral neuropathies causing the slow progression of sensory and distal muscle defects. Of note, the severity and progression of CMT symptoms markedly vary. The phenotypic heterogeneity of ALS and CMT suggests the existence of modifiers that determine disease characteristics. Epigenetic regulation of biological functions via gene expression without alterations in the DNA sequence may be an important factor. The methylation of DNA, noncoding RNA, and post-translational modification of histones are the major epigenetic mechanisms. Currently, Drosophila is emerging as a useful ALS and CMT model. In this review, we summarize recent studies linking ALS and CMT to epigenetic regulation with a strong emphasis on approaches using Drosophila models.

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Section: Epigenetic Regulation Of Cmtmentioning

confidence: 99%

Section: Epigenetic Regulation Of Cmtmentioning

confidence: 99%

Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models

Yamaguchi

Omori

Asada

et al. 2021

IJMS

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“…In D. melanogaster , two genes have been identified as human SLC25A46 homologs, CG8931 (named dSLC25A46a) and CG5755 (named dSLC25A46b); dSLC25A46a, if compared to dSLC25A46b, displays higher homology with the human SLC25A46 . Their physiological role has not yet been clarified, but they are predicted to be involved in mitochondrial membrane fission and in mitochondrial dynamics, like the human homolog [ 249 ]. In this regard, recently developed dSLC25A46a or dSLC25A46b knockdown Drosophila models displayed most of the phenotypes already observed in mitochondrial diseases caused by human SLC25A46 mutations.…”

Section: Drosophila Melanogaster Vs Human Mitomentioning

confidence: 99%

“…In particular, locomotor impairment and defects in neuromuscular junctions compromising synaptic function were observed in mutant fruit flies at different developmental stages. The knockdown of dSLC25A46a or dSLC25A46b also led to severe structural and functional mitochondrial defects, at least in part associated with ROS accumulation and ATP level reductions [ 249 , 250 ].…”

Section: Drosophila Melanogaster Vs Human Mitomentioning

confidence: 99%

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

Curcio

Lunetti

Zara

et al. 2020

IJMS

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Mitochondrial carriers are a family of structurally related proteins responsible for the exchange of metabolites, cofactors and nucleotides between the cytoplasm and mitochondrial matrix. The in silico analysis of the Drosophila melanogaster genome has highlighted the presence of 48 genes encoding putative mitochondrial carriers, but only 20 have been functionally characterized. Despite most Drosophila mitochondrial carrier genes having human homologs and sharing with them 50% or higher sequence identity, D. melanogaster genes display peculiar differences from their human counterparts: (1) in the fruit fly, many genes encode more transcript isoforms or are duplicated, resulting in the presence of numerous subfamilies in the genome; (2) the expression of the energy-producing genes in D. melanogaster is coordinated from a motif known as Nuclear Respiratory Gene (NRG), a palindromic 8-bp sequence; (3) fruit-fly duplicated genes encoding mitochondrial carriers show a testis-biased expression pattern, probably in order to keep a duplicate copy in the genome. Here, we review the main features, biological activities and role in the metabolism of the D. melanogaster mitochondrial carriers characterized to date, highlighting similarities and differences with their human counterparts. Such knowledge is very important for obtaining an integrated view of mitochondrial function in D. melanogaster metabolism.

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“…There are two SLC25A46 paralogues in Drosophila, SLC25A46a [ 53 ] and SLC25A46b [ 54 ]. Previous reports showed that knockdown of each of SLC25A46a and SLC25A46b in Drosophila similarly led to motor deficit such as reduced crawling and climbing abilities, a shortened synaptic length in the neuromuscular junction (NMJ), decreased ATP production and ROS accumulation [ 78 , 79 ].…”

Section: Drosophila Cmt Models For Investigatinmentioning

confidence: 99%

Recent Advances in Drosophila Models of Charcot-Marie-Tooth Disease

Kitani-Morii

Noto

2020

IJMS

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Charcot-Marie-Tooth disease (CMT) is one of the most common inherited peripheral neuropathies. CMT patients typically show slowly progressive muscle weakness and sensory loss in a distal dominant pattern in childhood. The diagnosis of CMT is based on clinical symptoms, electrophysiological examinations, and genetic testing. Advances in genetic testing technology have revealed the genetic heterogeneity of CMT; more than 100 genes containing the disease causative mutations have been identified. Because a single genetic alteration in CMT leads to progressive neurodegeneration, studies of CMT patients and their respective models revealed the genotype-phenotype relationships of targeted genes. Conventionally, rodents and cell lines have often been used to study the pathogenesis of CMT. Recently, Drosophila has also attracted attention as a CMT model. In this review, we outline the clinical characteristics of CMT, describe the advantages and disadvantages of using Drosophila in CMT studies, and introduce recent advances in CMT research that successfully applied the use of Drosophila, in areas such as molecules associated with mitochondria, endosomes/lysosomes, transfer RNA, axonal transport, and glucose metabolism.

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Neuron-specific knockdown of solute carrier protein SLC25A46a induces locomotive defects, an abnormal neuron terminal morphology, learning disability, and shortened lifespan

Cited by 11 publications

References 37 publications

Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models

Epigenetic Regulation of ALS and CMT: A Lesson from Drosophila Models

Drosophila melanogaster Mitochondrial Carriers: Similarities and Differences with the Human Carriers

Recent Advances in Drosophila Models of Charcot-Marie-Tooth Disease

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