The displacement of frataxin from the mitochondrial cristae correlates with abnormal respiratory supercomplexes formation and bioenergetic defects in cells of Friedreich ataxia patients.
FeS-cluster assembly
mitochondria
mitochondrial morphology
respiration
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
10
03
2020
revised:
09
12
2020
accepted:
28
12
2020
entrez:
25
2
2021
pubmed:
26
2
2021
medline:
27
7
2021
Statut:
ppublish
Résumé
Friedreich ataxia (FRDA) is a neurodegenerative disease resulting from a severe decrease of frataxin (FXN). Most patients carry a GAA repeat expansion in both alleles of the FXN gene, whereas a small fraction of them are compound heterozygous for the expansion and a point mutation in the other allele. FXN is involved in the mitochondrial biogenesis of the FeS-clusters. Distinctive feature of FRDA patient cells is an impaired cellular respiration, likely due to a deficit of key redox cofactors working as electrons shuttles through the respiratory chain. However, a definite relationship between FXN levels, FeS-clusters assembly dysregulation and bioenergetics failure has not been established. In this work, we performed a comparative analysis of the mitochondrial phenotype of cell lines from FRDA patients, either homozygous for the expansion or compound heterozygotes for the G130V mutation. We found that, in healthy cells, FXN and two key proteins of the FeS-cluster assembly machinery are enriched in mitochondrial cristae, the dynamic subcompartment housing the respiratory chain. On the contrary, FXN widely redistributes to the matrix in FRDA cells with defects in respiratory supercomplexes assembly and altered respiratory function. We propose that this could be relevant for the early mitochondrial defects afflicting FRDA cells and that perturbation of mitochondrial morphodynamics could in turn be critical in terms of disease mechanisms.
Identifiants
pubmed: 33629768
doi: 10.1096/fj.202000524RR
doi:
Substances chimiques
Electron Transport Chain Complex Proteins
0
Iron-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21362Informations de copyright
© 2021 Federation of American Societies for Experimental Biology.
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