Cross-compartment protection by SOD1

The absence of SOD1 in yeast has been found (M.A. Wallace et al., J. Biol. Chem. 279:32055–32062; 2004) to result in inactivation of Lys4p. This [4Fe-4S]-containing dehydratase is in the pathway of biosynthesis of lysine, hence the oxygen-dependent lysine auxotrophy seen in this case. O2− is known to oxidize and thus destabilize the [Fe–4S] clusters of dehydratases; hence, this would make perfect sense were it not for the fact that SOD1 localizes to the cytosol and the intermembrane space of mitochondria, whereas Lys4p localizes to the mitochondrial matrix. How could SOD1 in one compartment protect against O2− attack in a different compartment? We suggest that the relatively high levels of O2− in the cytosol and intermembrane space of the SOD1 mutant may react with endogenous NO, forming HOONO that can diffuse into the mitochondrial matrix and there inactivate Lys4p and other [4Fe–4S]-containing dehydratases.