Frontotemporal dementia-related V57E mutation impairs mitochondrial function and alters the structural properties of CHCHD10

Basit Öğe Kaydı
dc.authorid0000-0002-0772-9350
dc.contributor.authorAlıcı, Hakan
dc.contributor.authorUversky, Vladimir N.
dc.contributor.authorLiu, Tian
dc.contributor.authorKang, David E.
dc.contributor.authorWoo, Junga Alexa
dc.contributor.authorCoşkuner Weber, Orkid
dc.date.accessioned2024-05-07T07:11:32Z
dc.date.available2024-05-07T07:11:32Z
dc.date.issued2023
dc.departmentTAÜ, Fen Fakültesi, Moleküler Biyoteknoloji Bölümüen_US
dc.description.abstractThe V57E pathological variant of the mitochondrial coiled-coil-helix–coiled-coil-helix domain-containing protein 10 (CHCHD10) plays a role in frontotemporal dementia. The wild-type and V57E mutant CHCHD10 proteins contain intrinsically disordered regions, and therefore, these regions hampered structural characterization of these proteins using conventional experimental tools. For the first time in the literature, we represent that the V57E mutation is pathogenic to mitochondria as it increases mitochondrial superoxide and impairs mitochondrial respiration. In addition, we represent here the structural ensemble properties of the V57E mutant CHCHD10 and describe the impacts of V57E mutation on the structural ensembles of wild-type CHCHD10 in aqueous solution. We conducted experimental and computational studies for this research. Namely, MitoSOX Red staining and Seahorse Mito Stress experiments, atomic force microscopy measurements, bioinformatics, homology modeling, and multiple-run molecular dynamics simulation computational studies were conducted. Our experiments show that the V57E mutation results in mitochondrial dysfunction, and our computational studies present that the structural ensemble properties of wild-type CHCHD10 are impacted by the frontotemporal dementia-associated V57E genetic mutation.
dc.identifier.citationAlıcı, H., Uversky, Vladimir N., Liu, T., Kang, David E., Woo, Junga A., Coşkuner Weber, O. (2023). Frontotemporal dementia-related V57E mutation impairs mitochondrial function and alters the structural properties of CHCHD10. ACS Chemical Neuroscience.
dc.identifier.doi10.1021/acschemneuro.3c00125
dc.identifier.scopus2-s2.0-85160833122
dc.identifier.urihttps://pubs.acs.org/doi/10.1021/acschemneuro.3c00125
dc.identifier.urihttps://hdl.handle.net/20.500.12846/1227
dc.identifier.wosWOS:001005912900001
dc.indekslendigikaynakScopus
dc.language.isoen
dc.relation.ispartofACS Chemical Neuroscience
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectG58Ren_US
dc.subjectGeneticsen_US
dc.subjectCHCHD10en_US
dc.subjectMitochondrial myopathyen_US
dc.subjectStructural propertiesen_US
dc.subjectMultiple-run molecular dynamics simulationsen_US
dc.subjectBioinformaticsen_US
dc.titleFrontotemporal dementia-related V57E mutation impairs mitochondrial function and alters the structural properties of CHCHD10
dc.typeArticle

Dosyalar

Orijinal paket
Listeleniyor 1 - 2 / 2
Küçük Resim
İsim:
cn3c00125_si_001.pdf
Boyut:
5.99 MB
Biçim:
Adobe Portable Document Format
Açıklama:
Makale Dosyası
İndir
Küçük Resim
İsim:
acncdm.2023.14.issue-11.largecover.jpg
Boyut:
103.49 KB
Biçim:
Joint Photographic Experts Group/JPEG File Interchange Format (JFIF)
Açıklama:
Kitap Kapağı
İndir
Lisans paketi
Listeleniyor 1 - 1 / 1
[ X ]
İsim:
license.txt
Boyut:
1.44 KB
Biçim:
Item-specific license agreed upon to submission
Açıklama:
İndir

Koleksiyon

Moleküler Biyoteknoloji
Scopus İndeksli Yayınlar Koleksiyonu