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  1. Article ; Online: Epitranscriptomics in metabolic disease.

    Matsumura, Yoshihiro / Wei, Fan-Yan / Sakai, Juro

    Nature metabolism

    2023  Volume 5, Issue 3, Page(s) 370–384

    Abstract: While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene ... ...

    Abstract While epigenetic modifications of DNA and histones play main roles in gene transcription regulation, recently discovered post-transcriptional RNA modifications, known as epitranscriptomic modifications, have been found to have a profound impact on gene expression by regulating RNA stability, localization and decoding efficiency. Importantly, genetic variations or environmental perturbations of epitranscriptome modifiers (that is, writers, erasers and readers) are associated with obesity and metabolic diseases, such as type 2 diabetes. The epitranscriptome is closely coupled to epigenetic signalling, adding complexity to our understanding of gene expression in both health and disease. Moreover, the epitranscriptome in the parental generation can affect organismal phenotypes in the next generation. In this Review, we discuss the relationship between epitranscriptomic modifications and metabolic diseases, their relationship with the epigenome and possible therapeutic strategies.
    MeSH term(s) Humans ; Diabetes Mellitus, Type 2/genetics ; Metabolic Diseases/genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; RNA Processing, Post-Transcriptional
    Language English
    Publishing date 2023-03-23
    Publishing country Germany
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-023-00764-4
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  2. Article ; Online: Protocol for preparation and measurement of intracellular and extracellular modified RNA using liquid chromatography-mass spectrometry

    Akiko Ogawa / Fan-Yan Wei

    STAR Protocols, Vol 2, Iss 4, Pp 100848- (2021)

    2021  

    Abstract: Summary: About 150 modifications have been identified in RNA species. Besides their regulatory roles in the intracellular gene expression, abundant modified RNA nucleosides are catabolized from RNA and released into extracellular fluids, which can impact ...

    Abstract Summary: About 150 modifications have been identified in RNA species. Besides their regulatory roles in the intracellular gene expression, abundant modified RNA nucleosides are catabolized from RNA and released into extracellular fluids, which can impact extracellular signaling as ligands for receptors. Here, we describe a protocol to prepare samples from biological specimens, including cultured cells, extracellular fluid, and tissues, to measure both intracellular and extracellular RNA modifications using mass spectrometry.For complete details on the use and execution of this protocol, please refer to Ogawa et al. (2021).
    Keywords Mass Spectrometry ; Metabolism ; Metabolomics ; Molecular Biology ; Signal Transduction ; Science (General) ; Q1-390
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with age‐related hearing loss

    Toru Miwa / Tatsuya Katsuno / Fan‐Yan Wei / Kazuhito Tomizawa

    FEBS Open Bio, Vol 13, Iss 7, Pp 1365-

    2023  Volume 1374

    Abstract: Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea ... ...

    Abstract Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification‐induced hearing loss and mitochondrial dysfunction.
    Keywords age‐related hearing loss ; Cdk5rap1 ; microstructural findings ; mitochondria ; mitochondrial tRNA ; transmission electron microscopy ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
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  4. Article ; Online: Protocol for preparation and measurement of intracellular and extracellular modified RNA using liquid chromatography-mass spectrometry.

    Ogawa, Akiko / Wei, Fan-Yan

    STAR protocols

    2021  Volume 2, Issue 4, Page(s) 100848

    Abstract: About 150 modifications have been identified in RNA species. Besides their regulatory roles in the intracellular gene expression, abundant modified RNA nucleosides are catabolized from RNA and released into extracellular fluids, which can impact ... ...

    Abstract About 150 modifications have been identified in RNA species. Besides their regulatory roles in the intracellular gene expression, abundant modified RNA nucleosides are catabolized from RNA and released into extracellular fluids, which can impact extracellular signaling as ligands for receptors. Here, we describe a protocol to prepare samples from biological specimens, including cultured cells, extracellular fluid, and tissues, to measure both intracellular and extracellular RNA modifications using mass spectrometry. For complete details on the use and execution of this protocol, please refer to Ogawa et al. (2021).
    MeSH term(s) Cells, Cultured ; Chromatography, Liquid/methods ; Mass Spectrometry/methods ; Nucleosides/analysis ; RNA/genetics
    Chemical Substances Nucleosides ; RNA (63231-63-0)
    Language English
    Publishing date 2021-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2021.100848
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with age-related hearing loss.

    Miwa, Toru / Katsuno, Tatsuya / Wei, Fan-Yan / Tomizawa, Kazuhito

    FEBS open bio

    2023  Volume 13, Issue 7, Page(s) 1365–1374

    Abstract: Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea ... ...

    Abstract Previous studies have revealed that age-related hearing loss (AHL) in Cdk5 regulatory subunit-associated protein 1 (Cdk5rap1)-knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1-knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification-induced hearing loss and mitochondrial dysfunction.
    MeSH term(s) Animals ; Mice ; Cochlea/metabolism ; Cochlea/pathology ; Hearing Loss/genetics ; Hearing Loss/metabolism ; Hearing Loss/pathology ; Mice, Knockout ; Mitochondria/genetics ; Mitochondria/metabolism
    Chemical Substances Cdk5rap1 protein, mouse (EC 2.8.-) ; Cdk5r1 protein, mouse
    Language English
    Publishing date 2023-06-06
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2651702-4
    ISSN 2211-5463 ; 2211-5463
    ISSN (online) 2211-5463
    ISSN 2211-5463
    DOI 10.1002/2211-5463.13655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Posttranscriptional modifications in mitochondrial tRNA and its implication in mitochondrial translation and disease.

    Kazuhito, Tomizawa / Wei, Fan-Yan

    Journal of biochemistry

    2020  Volume 168, Issue 5, Page(s) 435–444

    Abstract: A fundamental aspect of mitochondria is that they possess DNA and protein translation machinery. Mitochondrial DNA encodes 22 tRNAs that translate mitochondrial mRNAs to 13 polypeptides of respiratory complexes. Various chemical modifications have been ... ...

    Abstract A fundamental aspect of mitochondria is that they possess DNA and protein translation machinery. Mitochondrial DNA encodes 22 tRNAs that translate mitochondrial mRNAs to 13 polypeptides of respiratory complexes. Various chemical modifications have been identified in mitochondrial tRNAs via complex enzymatic processes. A growing body of evidence has demonstrated that these modifications are essential for translation by regulating tRNA stability, structure and mRNA binding, and can be dynamically regulated by the metabolic environment. Importantly, the hypomodification of mitochondrial tRNA due to pathogenic mutations in mitochondrial tRNA genes or nuclear genes encoding modifying enzymes can result in life-threatening mitochondrial diseases in humans. Thus, the mitochondrial tRNA modification is a fundamental mechanism underlying the tight regulation of mitochondrial translation and is essential for life. In this review, we focus on recent findings on the physiological roles of 5-taurinomethyl modification (herein referred as taurine modification) in mitochondrial tRNAs. We summarize the findings in human patients and animal models with a deficiency of taurine modifications and provide pathogenic links to mitochondrial diseases. We anticipate that this review will help understand the complexity of mitochondrial biology and disease.
    MeSH term(s) Animals ; Humans ; Mitochondria/genetics ; Mitochondria/metabolism ; Mitochondrial Diseases/genetics ; Mitochondrial Diseases/metabolism ; Mitochondrial Diseases/pathology ; RNA Processing, Post-Transcriptional ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Taurine/metabolism
    Chemical Substances Taurine (1EQV5MLY3D) ; RNA, Transfer (9014-25-9)
    Language English
    Publishing date 2020-08-20
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 218073-x
    ISSN 1756-2651 ; 0021-924X
    ISSN (online) 1756-2651
    ISSN 0021-924X
    DOI 10.1093/jb/mvaa098
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with age‐related hearing loss

    Miwa, Toru / Katsuno, Tatsuya / Wei, Fan‐Yan / Tomizawa, Kazuhito

    FEBS Open Bio. 2023 July, v. 13, no. 7 p.1365-1374

    2023  

    Abstract: Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea ... ...

    Abstract Previous studies have revealed that age‐related hearing loss (AHL) in Cdk5 regulatory subunit‐associated protein 1 (Cdk5rap1)‐knockout mice is associated with pathology in the cochlea. Here, we aimed to identify mitochondrial alterations in the cochlea of Cdk5rap1‐knockout mice with AHL. Mitochondria in the spiral ganglion neurons (SGNs) and hair cells (HCs) were normal despite senescence; however, the mitochondria of types I, II, and IV spiral ligament fibrocytes were ballooned, damaged, and ballooned, respectively, in the stria vascularis. Our results suggest that the accumulation of dysfunctional mitochondria in the lateral wall, rather than the loss of HCs and SGNs, leads to the onset of AHL. Our results provide valuable information regarding the underlying mechanisms of AHL and the relationship between aberrant tRNA modification‐induced hearing loss and mitochondrial dysfunction.
    Keywords ganglia ; ligaments ; mitochondria
    Language English
    Dates of publication 2023-07
    Size p. 1365-1374.
    Publishing place John Wiley & Sons, Ltd
    Document type Article ; Online
    Note JOURNAL ARTICLE
    ZDB-ID 2651702-4
    ISSN 2211-5463
    ISSN 2211-5463
    DOI 10.1002/2211-5463.13655
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  8. Article ; Online: Supersulfide biology and translational medicine for disease control.

    Barayeu, Uladzimir / Sawa, Tomohiro / Nishida, Motohiro / Wei, Fan-Yan / Motohashi, Hozumi / Akaike, Takaaki

    British journal of pharmacology

    2023  

    Abstract: For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, contributing to energy production in aerobic organisms. ... ...

    Abstract For decades, the major focus of redox biology has been oxygen, the most abundant element on Earth. Molecular oxygen functions as the final electron acceptor in the mitochondrial respiratory chain, contributing to energy production in aerobic organisms. In addition, oxygen-derived reactive oxygen species including hydrogen peroxide and nitrogen free radicals, such as superoxide, hydroxyl radical and nitric oxide radical, undergo a complicated sequence of electron transfer reactions with other biomolecules, which lead to their modified physiological functions and diverse biological and pathophysiological consequences (e.g. oxidative stress). What is now evident is that oxygen accounts for only a small number of redox reactions in organisms and knowledge of biological redox reactions is still quite limited. This article reviews a new aspects of redox biology which is governed by redox-active sulfur-containing molecules-supersulfides. We define the term 'supersulfides' as sulfur species with catenated sulfur atoms. Supersulfides were determined to be abundant in all organisms, but their redox biological properties have remained largely unexplored. In fact, the unique chemical properties of supersulfides permit them to be readily ionized or radicalized, thereby allowing supersulfides to actively participate in redox reactions and antioxidant responses in cells. Accumulating evidence has demonstrated that supersulfides are indispensable for fundamental biological processes such as energy production, nucleic acid metabolism, protein translation and others. Moreover, manipulation of supersulfide levels was beneficial for pathogenesis of various diseases. Thus, supersulfide biology has opened a new era of disease control that includes potential applications to clinical diagnosis, prevention and therapeutics of diseases.
    Language English
    Publishing date 2023-10-23
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80081-8
    ISSN 1476-5381 ; 0007-1188
    ISSN (online) 1476-5381
    ISSN 0007-1188
    DOI 10.1111/bph.16271
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    Uf I Zs.146: Show issues Location:
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  9. Article ; Online: Cdk5 regulatory subunit-associated protein 1 knockout mice show hearing loss phenotypically similar to age-related hearing loss.

    Miwa, Toru / Wei, Fan-Yan / Tomizawa, Kazuhito

    Molecular brain

    2021  Volume 14, Issue 1, Page(s) 82

    Abstract: Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables ... ...

    Abstract Mitochondrial dysfunction is associated with aging and age-related hearing loss (AHL). However, the precise mechanisms underlying the pathophysiology of hearing loss remain unclear. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) enables efficient intramitochondrial translation by catalyzing the deposition of 2-methylthio modifications on mitochondrial tRNAs. Here we investigated the effect of defective mitochondrial protein translation on hearing and AHL in a Cdk5rap1 deficiency C57BL/6 mouse model. Compared to control C57BL/6 mice, Cdk5rap1-knockout female mice displayed hearing loss phenotypically similar to AHL from an early age. The premature hearing loss in Cdk5rap1-knockout mice was associated with the degeneration of the spiral ligament and reduction of endocochlear potentials following the loss of auditory sensory cells. Furthermore, cultured primary mouse embryonic fibroblasts displayed early onset of cellular senescence associated with high oxidative stress and cell death. These results indicate that the CDK5RAP1 deficiency-induced defective mitochondrial translation might cause early hearing loss through the induction of cellular senescence and cochlear dysfunction in the inner ear. Our results suggest that the accumulation of dysfunctional mitochondria might promote AHL progression. Furthermore, our findings suggest that mitochondrial dysfunction and dysregulated mitochondrial tRNA modifications mechanistically cause AHL. Understanding the mechanisms underlying AHL will guide future clinical investigations and interventions in the attempt to mitigate the consequences of AHL.
    MeSH term(s) Action Potentials ; Aging/pathology ; Animals ; Apoptosis ; Cell Cycle Proteins/deficiency ; Cell Cycle Proteins/metabolism ; Female ; Fibroblasts/metabolism ; Hair Cells, Auditory/metabolism ; Metabolome ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism ; Mitochondria/ultrastructure ; Mitochondrial Proteins/genetics ; Phenotype ; Presbycusis/genetics ; Reactive Oxygen Species/metabolism ; Spiral Ganglion/metabolism ; Spiral Ligament of Cochlea/metabolism ; Stress, Physiological ; Stria Vascularis/metabolism ; Sulfur Group Transferases/genetics ; Mice
    Chemical Substances Cell Cycle Proteins ; Mitochondrial Proteins ; Reactive Oxygen Species ; Cdk5rap1 protein, mouse (EC 2.8.-) ; Sulfur Group Transferases (EC 2.8.-)
    Language English
    Publishing date 2021-05-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2436057-0
    ISSN 1756-6606 ; 1756-6606
    ISSN (online) 1756-6606
    ISSN 1756-6606
    DOI 10.1186/s13041-021-00791-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: 

    Su, Fan / Qin, Xiao-Wei / Fan, Rui / Yan, Lin / Ji, Xun-Zhi / Hao, Chao-Yun

    PhytoKeys

    2024  Volume 238, Page(s) 85–94

    Abstract: ... ...

    Abstract Pipermotuoense
    Language English
    Publishing date 2024-02-07
    Publishing country Bulgaria
    Document type Journal Article
    ZDB-ID 2579891-1
    ISSN 1314-2003 ; 1314-2011
    ISSN (online) 1314-2003
    ISSN 1314-2011
    DOI 10.3897/phytokeys.238.115494
    Database MEDical Literature Analysis and Retrieval System OnLINE

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