A Theoretical Model of Mitochondrial ATP Synthase Deficiencies. The Role of Mitochondrial Carriers

The m.8993T>G mutation of the mitochondrial MT-ATP6 gene is associated with NARP syndrome (neuropathy, ataxia and retinitis pigmentosa). equivalent point introduced in yeast Saccharomyces cerevisiae DNA considerably reduced activity ATP synthase cytochrome-c-oxidase, preventing growth on oxidative substrates. overexpression oxodicarboxylate carrier (Odc1p) was able to rescue substrate by increasing substrate-level phosphorylation ADP coupled conversion ?-ketoglutarate (AKG) into succinate an increase Complex IV activity. Previous studies showed that mutations behave similarly can be rescued Odc1p and/or uncoupling OXPHOS from synthesis. In order better understand mechanism bypass, we developed a core model metabolism based AKG as respiratory substrate. We describe different possible metabolite outputs ATP/O ratio values function inhibition.