PuSH - Publikationsserver des Helmholtz Zentrums München: Impaired complex I repair causes recessive Leber's hereditary optic neuropathy.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Stenton, S. ; Sheremet, N.L.* ; Catarino, C.B.* ; Andreeva, N.* ; Assouline, Z.* ; Barboni, P.* ; Barel, O.* ; Berutti, R. ; Bychkov, I.O.* ; Caporali, L.* ; Capristo, M.* ; Carbonelli, M.* ; Cascavilla, M.L.* ; Charbel Issa, P.* ; Freisinger, P.* ; Gerber, S.* ; Ghezzi, D.* ; Graf, E. ; Heidler, J.* ; Hempel, M.* ; Héon, E.* ; Itkis, Y.S.* ; Javasky, E.* ; Kaplan, J.* ; Kopajtich, R. ; Kornblum, C.* ; Kovács-Nagy, R.* ; Krylova, T.* ; Kunz, W.S.* ; La Morgia, C.* ; Lamperti, C.* ; Ludwig, C.* ; Malacarne, P.F.* ; Maresca, A.* ; Mayr, J.A.* ; Meisterknecht, J.* ; Nevinitsyna, T.* ; Palombo, F.* ; Pode-Shakked, B.* ; Shmelkova, M.S.* ; Strom, T.M.* ; Tagliavini, F.* ; Tzadok, M.* ; van der Ven, A.T.* ; Vignal-Clermont, C.* ; Wagner, M. ; Zakharova, E.* ; Zhorzholadze, N.* ; Rozet, J.M.* ; Carelli, V.* ; Tsygankova, P.* ; Klopstock, T.* ; Wittig, I.* ; Prokisch, H.

Impaired complex I repair causes recessive Leber's hereditary optic neuropathy.

J. Clin. Invest. 131:e138267 (2021)

Verlagsversion

Postprint

DOI

PMC

	Open Access Hybrid

Abstract
Metriken
Zusatzinfos

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in the mitochondrial DNA (mtDNA). A molecular diagnosis is reached in up to 95%, the vast majority of which are accounted for by three mutations within mitochondrial complex I (CI) subunit encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON are recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knock-out cellular model, we measure reduced turnover of specific CI N-module subunits and a resultant impairment of CI function. This demonstrates DNAJC30 is to be a chaperone protein needed for the efficient exchange of CI subunits exposed to reactive oxygen species and integral to a mitochondrial CI repair mechanism, thereby providing the first example of a disease resulting from impaired exchange of assembled respiratory chain subunits.

Impact Factor

Scopus SNIP

Scopus
Cited By

Altmetric

14.808

0.000