Glial-specific mitochondrial failure and redox imbalance contribute to regional vulnerability in Friedreich's ataxia

Arabela Sanz-Alcázar, Marta Portillo-Carrasquer, Israel Manjarres-Raza, Maria Pazos-Gil, Fabien Delaspre, Jordi Tamarit, Juan P. Bolaños, Joaquim Ros, Elisa Cabiscol, Glial-specific mitochondrial failure and redox imbalance contribute to regional vulnerability in Friedreich's ataxia, Redox Biology, Volume 98, 2026, 104437, ISSN 2213-2317, doi:10.1016/j.redox.2026.104437. 

Highlights: Glial dysfunction, not neuronal failure, is linked to regional degeneration in FA. Satellite glia and sensory neurons show early iron overload and oxidative stress. Astrocytic dysfunction precedes neuronal pathology in the cerebrum and cerebellum. Mitochondrial impairment and iron overload contribute to cell-specific ferroptosis. NRF2-GPX4 axis collapse is associated with disease progression in FA.

Glial-specific mitochondrial failure and redox imbalance contribute to regional vulnerability in Friedreich's ataxia