Life by a new decarboxylation-dependent energy conservation mechanism with Na+ as coupling ion

We report here a new mode of ATP synthesis in living cells. The anaerobic bacterium Propionigenium modestum gains its total energy for growth from the conversion of succinate to propionate according to: succinate + H20 → propionate + HCO3 - (AGOI = -20.6 kJ/mol). The small free energy change of this reaction does not allow a substrate-linked phosphorylation mechanism, and no electron transport phosphorylation takes place. Succinate was degraded by cell-free extracts to propionate and CO2 via succinyl-CoA, methylmalonyl- CoA and propionyl-CoA. This pathway involves a membrane-bound methylmalonyl-CoA decarboxylase which couples the exergonic decarboxylation with a Na + ion transport across the membrane. The organism also contained a membrane-bound ATPase which was specifically activated by Na + ions and catalyzed the transport of Na + ions into inverted bacterial vesicles upon ATP hydrolysis. The transport was abolished by monensin but not by the uncoupler carbonylcyanide- p-trifluoromethoxy phenylhydrazone. Isolated membrane vesicles catalyzed the synthesis of ATP from ADP and inorganic phosphate when malonyl-CoA was decarboxylated and malonyl-CoA synthesis from acetyl-CoA when ATP was hydrolyzed. These syntheses were sensitive to monensin which indicates that Na + functions as the coupling ion. We conclude from these results that ATP synthesis in P. modestum is driven by a Na + ion gradient which is generated upon decarboxylation of methylmalonyl-CoA