Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria

Abstract

The catalytic domain of the F-ATPase in mitochondria protrudes into the matrix of the organelle, and is attached to the membrane domain by central and peripheral stalks. Energy for the synthesis of ATP from ADP and phosphate is provided by the transmembrane proton-motive-force across the inner membrane, generated by respiration. The proton-motive force is coupled mechanically to ATP synthesis by the rotation at about 100 times per second of the central stalk and an attached ring of c-subunits in the membrane domain. Each c-subunit carries a glutamate exposed around the midpoint of the membrane on the external surface of the ring. The rotation is generated by protonation and deprotonation successively of each glutamate. Each 360°rotation produces three ATP molecules, and requires the translocation of one proton per glutamate by each c-subunit in the ring. In fungi, eubacteria, and plant chloroplasts, ring sizes of c 10

ATP synthase: From sequence to ring size to the P/O ratio

“…The c subunits adopt a hairpin helical structure with the N-terminal helix contributing to the smaller circumference inner ring. Structural and bioinformatic analysis conducted by Walker and colleagues (1) indicates that attempts to model a c 8 ring by using a yeast sequence and structure result in serious stereochemical clashes among the side chains of residues Ile-13, Leu-19, and Ile-23 of adjacent protomers in the hypothetical ring. Notably, each of these residues is replaced, with one exception, by alanine in all animalia species.…”

“…Furthermore, mitochondria might be damaged, either homogeneously or heterogeneously, and thus provide underestimates of the P/O ratio because O 2 consumption can proceed without full coupling to ATP synthesis, e.g., owing to leakage of protons across membranes. The combatants in the P/O battles of the 1950s could never have imagined that P/O ratios might be assessed via structural biology, as illustrated by a study (1) in PNAS. Many biochemists also have not contemplated that a highly conserved enzyme has a variable relative subunit stoichiometry.…”

Engineering rotor ring stoichiometries in the ATP synthase

“…The number of c-subunits (n) per c n ring appears to be fixed for a given species, but this stoichiometry varies across different species (Table S1). Based on all F-type ATP synthases known to date, the range spans from n = 8 (9) to n = 15 (10). Each c-subunit contributes to create one binding site for one coupling ion (H + or Na + ) (11,12), which is translocated across the membrane (13).…”

Operation mechanism of FoF1‐adenosine triphosphate synthase revealed by its structure and dynamics

“…Bacterial F o has a subunit stoichiometry of ab 2 c 10-15 (in F o from bovine mitochondria, stoichiometry of eight c-subunits has been reported recently (34)). The c-subunit has a hairpin structure, which is composed of two a-helices and a connecting loop.…”

“…The c-subunit has a hairpin structure, which is composed of two a-helices and a connecting loop. Crystal structures of the F 1 -c-ring (34,35) and isolated c-ring (36)(37)(38) revealed that the c-subunits form a ring complex by assembling in a circle with the C-terminus pointing outward and the connecting loop toward the F 1 side (cytoplasmic side in bacteria) (Fig. 4).…”