Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia

Chandra S, Kwak C, Du Z ... Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia, Cell Chemical Biology, 2026; 0.  DOI: 10.1016/j.chembiol.2026.05.004

MR3 treatment modulates molecular signatures in a cell-type-dependent manner, altering pathways related to cardiac contractility in cardiomyocytes and synaptic function in sensory neurons. Mechanistically, MR3 reduces mitochondrial reactive oxygen species and restores membrane potential in FA sensory neurons via potential allosteric reshaping of Miro1 protein. We expand the chemical diversity of this scaffold by conducting ligand-based virtual screening of over 3 billion compounds and identifying previously uncharacterized Miro1 ligands with improved docking and neuroprotective capacity.

Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich’s ataxia