Promotion of oxidative phosphorylation by complex-I-anchored carbonic anhydrases?

•Recent high-resolution cryoEM maps gave detailed insights into the arrangement of the carbonic anhydrase module next to a ferredoxin subunit and a proton translocation channel of plant, algal and protozoan mitochondrial complex I.•Complex I anchored carbonic anhydrase may promote the provision of protons at the inside of the inner mitochondrial membrane, thereby supporting oxidative phosphorylation.•The cryoEM maps imply that a possible local pH difference between the active site of the CA module and the positive charge of a ferredoxin bound single iron or iron-sulfur cluster facilitates the migration of protons to the entrance of a proton translocation channel at complex I.•In the context of early endosymbiosis with mitochondria lacking cristae invaginations that shield off high proton leakage, complex I bound carbonic anhydrases might have ensured maintenance of OXPHOS. The mitochondrial NADH-dehydrogenase complex of the respiratory chain, known as complex I, includes a carbonic anhydrase (CA) module attached to its membrane arm on the matrix side in protozoans, algae and plants. Its physiological role is so far unclear. Recent cryoEM structures show that the CA module may directly provide protons for translocation across the inner mitochondrial membrane at complex I. Carbonic anhydrases can play a central role in adjusting the proton concentration in the mitochondrial matrix. We suggest that CA-anchoring in complex I represents the original configuration to secure Oxidative Phosphorylation in the context of early endosymbiosis. After development of “modern mitochondria” with pronounced cristae structures, this anchoring became dispensable, but has been retained in protozoans, algae and plants. The mitochondrial NADH-dehydrogenase complex of the respiratory chain, known as complex I, includes a carbonic anhydrase (CA) module attached to its membrane arm on the matrix side in protozoans, algae and plants. Its physiological role is so far unclear. Recent cryoEM structures show that the CA module may directly provide protons for translocation across the inner mitochondrial membrane at complex I. Carbonic anhydrases can play a central role in adjusting the proton concentration in the mitochondrial matrix. We suggest that CA-anchoring in complex I represents the original configuration to secure Oxidative Phosphorylation in the context of early endosymbiosis. After development of “modern mitochondria” with pronounced cristae structures, this anchoring became