Energy conservation and uncoupling in mitochondria

Abstract

Energy conservation and uncoupling in mitochondria are examined in the light of three important new findings: (a) Studies with the photoaffinity‐labeling uncoupler 2‐azido‐4‐nitrophenol have shown that mitochondria contain a specific uncoupler binding site (apparently a polypeptide of M_r = 30,000 ± 10%). (b) This site fractionates into an enzyme complex (complex V), which is capable of oligomycin‐ and uncoupler‐sensitive ATP‐Pi exchange. It is absent from electron transfer complexes I, III, and IV, which represent segments of the respiratory chain containing coupling sites 1, 2, and 3, respectively. (c) Trinitrophenol is a membrane‐impermeable uncoupler (uncouples submitochondrial particles, but not mitochondria) and a poor protonophore. There is an excellent correlation between the uncoupling potencies and the affinities of uncouplers for the mitochondrial uncoupler‐binding site. There is no correlation between uncoupling potency and protonophoric activity of uncouplers when a membrane‐permeable uncoupler is compared with a membrane‐impermeable one.