PZL-A is a first-in-class activator of mammalian mitochondrial DNA (mtDNA). AC50s: 160 nM for A467T mutant, 20 nM for G848S mutant. mtDNA, which encodes essential protein subunits of the oxidative phosphorylation complexes, is replicated by DNA polymerase POLgamma. PZL-A restores function to mutant POLgamma via binding to an allosteric site between the catalytic subunits POLgammaA and POLgammaB. An important new tool for studying mitochondrial disorders.
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