PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Sung, A.Y.* ; Guerra, R.M.* ; Steenberge, L.H.* ; Alston, C.L.* ; Murayama, K.* ; Okazaki, Y.* ; Shimura, M. ; Prokisch, H. ; Ghezzi, D.* ; Torraco, A.* ; Carrozzo, R.* ; Rötig, A.* ; Taylor, R.W.* ; Keck, J.L.* ; Pagliarini, D.J.*

Systematic analysis of NDUFAF6 in complex I assembly and mitochondrial disease.

Nat. Metab., DOI: 10.1038/s42255-024-01039-2 (2024)
Postprint Forschungsdaten DOI PMC
Open Access Green
Isolated complex I (CI) deficiencies are a major cause of primary mitochondrial disease. A substantial proportion of CI deficiencies are believed to arise from defects in CI assembly factors (CIAFs) that are not part of the CI holoenzyme. The biochemistry of these CIAFs is poorly defined, making their role in CI assembly unclear, and confounding interpretation of potential disease-causing genetic variants. To address these challenges, we devised a deep mutational scanning approach to systematically assess the function of thousands of NDUFAF6 genetic variants. Guided by these data, biochemical analyses and cross-linking mass spectrometry, we discovered that the CIAF NDUFAF6 facilitates incorporation of NDUFS8 into CI and reveal that NDUFS8 overexpression rectifies NDUFAF6 deficiency. Our data further provide experimental support of pathogenicity for seven novel NDUFAF6 variants associated with human pathology and introduce functional evidence for over 5,000 additional variants. Overall, our work defines the molecular function of NDUFAF6 and provides a clinical resource for aiding diagnosis of NDUFAF6-related diseases.
Impact Factor
Scopus SNIP
Altmetric
19.200
0.000
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Leigh-syndrome; Association; Deficiency; Mutations; Mechanism; Sequences; Enzymes; Genes; Cells
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Zeitschrift Nature metabolism
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
G-503292-001
Förderungen NIH Roadmap for Medical Research
NIH
BJC Investigator Program
NIHR
Wellcome Centre for Mitochondrial Research
Mitochondrial Disease Patient Cohort grant
Medical Research Council International Centre for Genomic Medicine in Neuromuscular Disease
Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development
Italian Ministry of Health
German Federal Ministry of Education and Research
European Joint Programme on Rare Diseases project GENOMIT
NCI Cancer Center Support Grant
Siteman Cancer Center from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH)
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
DOI 10.1038/s42255-024-01039-2
WOS ID 001216061400002
Scopus ID 85192529648
PubMed ID 38720117
Erfassungsdatum 2024-06-11
[➜Korrektur melden]