Oxidative phosphorylation

Borisov and Forte describe the mammalian respiratory chain as unbranched. It has four membrane-bound complexes: NADH dehydrogenase, succinate dehydrogenase, the cytochrome bc1 complex and cytochrome c oxidase. The chain carries electrons from NADH and succinate to oxygen. The steps at complexes I, III and IV are coupled to the proton motive force, which ATP synthase uses to make ATP.⁶ Morse and colleagues give the same sequence. They state that the force has two parts, a pH gradient and a membrane potential.⁹ Wallace noted that fungal and animal mitochondrial DNA keep essentially the same set of OXPHOS polypeptide genes. In mammals these are a small share of each complex, for example seven of about 45 polypeptides in complex I.¹

Brzezinski, Moe and Ädelroth describe where the machinery sits. In mitochondria the respiratory chain lies in the flat regions of the cristae, while the ATP synthases are restricted mainly to the bent end regions. In aerobic bacteria the chain sits in the cytoplasmic membrane.⁷ The same authors separate yield, the ATP formed per amount of substrate oxidised, from efficiency. They state that yield depends on every component, including ATP synthase. They therefore do not expect it to change when respiratory complexes associate into supercomplexes.⁸ Protasoni and Zeviani put the complete oxidation of one glucose molecule at 30 ATP.⁵

Preiss and colleagues reported that alkaliphilic aerobes grow non-fermentatively on energy from proton-pumping respiratory chains. These bacteria complete oxidative phosphorylation with proton-coupled ATP synthases. The authors say this finding has challenged a tenet of the formal Mitchellian chemiosmotic hypothesis.² The point appears in a review of industrial uses of these bacteria. They do not argue for settling it with a narrow thermodynamic solution alone. They suggest looking at the broader physiology of alkaliphiles, which may have evolved many adaptations that together support their extreme lifestyle.²

Kaludercic and Giorgio report that ATP synthase is susceptible to reactive oxygen species in vitro. They also link it to oxidative and nitrosative stress in disorders of the central nervous system and in aging. They suggest that such modifications of oxidative phosphorylation efficiency may explain mitochondrial involvement in neurological disease.³ They describe a study by Ni and colleagues in diabetic mouse hearts. There calpain-1 degrades the alpha subunit, ATP synthase activity falls and mitochondrial superoxide rises. Blocking calpain-1 or raising the alpha subunit reversed these changes. Kaludercic and Giorgio think that, besides too little ATP, electrons accumulate upstream and promote superoxide formation at complexes I and III.⁴