Highlights d Lack of reactive oxygen species, or reductive stress, prevents myogenesis d Reductive stress reverses oxidation of invariant Cys residues in FNIP1 d Only reduced, but not oxidized, FNIP1 is polyubiquitylated by CUL2 FEM1B d FNIP1 degradation leads to activation of mitochondria to recalibrate ROS
Highlights d CUL2 FEM1B recognizes reduced FNIP1 through two interface zinc ions d Zn 2+ is essential for reductive stress signaling d FNIP1 access to CUL2 FEM1B is gated by BEX protein pseudosubstrate inhibitors d Mutation of FEM1B and BEX deletion cause similar developmental syndromes
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