The displacement of frataxin from the mitochondrial cristae correlates with abnormal respiratory supercomplexes formation and bioenergetic defects in cells of Friedreich ataxia patients

Davide Doni, Giovanni Rigoni, Elisa Palumbo, Elisa Baschiera, Roberta Peruzzo, Edith De Rosa, Federico Caicci, Leonardo Passerini, Daniela Bettio, Antonella Russo, Ildiko Szabò, Maria Eugenia Soriano, Leonardo Salviati, Paola Costantini; The FASEB Journal. 2021; 35:e21362. doi:10.1096/fj.202000524RR

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.