Quinone pool, ubiquinone diffusion and electron transfer between respiratory complexes

Kühlbrandt (2015) describes complex I as feeding electrons from NADH to a quinol in the membrane, with the released energy used to pump protons.¹ Brzezinski, Moe and Ädelroth (2021) add that succinate dehydrogenase also reduces quinone. They note that yeasts such as S. cerevisiae, which lack complex I, use other NADH dehydrogenases for the same step.⁵ They state that the reduced QH2 diffuses within the membrane to complex III.⁵ Protasoni and Zeviani (2021) describe the quinone in three redox forms: ubiquinone, semiquinone and ubiquinol. At complex III the Qo site oxidises ubiquinol and the Qi site reduces ubiquinone.⁶

Sousa, Mills, Vonck and Kühlbrandt (2016) examined the bovine respirasome. They report that the quinol oxidation site of the active complex III monomer faces the quinol release site of complex I, about 11 nm away.² The site of the inactive monomer lies at least 18 nm away, assuming quinol cannot pass through the dimer.² A quinol diffusing in the bilayer would therefore meet the active monomer first, which they suggest may explain why only that monomer is active.² They also note that substrate channeling has been extensively debated, and that Blaza et al. (2014) reported results inconsistent with distinct quinone pools.²

Fedor and Hirst (2018) set out a test. If supercomplexes contain and channel quinone, a competing quinol oxidase outside the supercomplex should not be able to turn over.³ They added alternative oxidase (AOX) to mammalian respiratory membranes and followed NADH oxidation. AOX bound to the membranes and catalysed quinol oxidation immediately.³ Protasoni and Zeviani (2021) summarise a similar AOX experiment in bovine heart mitochondria. A separate respirasome pool should keep a substantial electron flux. Instead, increasing AOX produced competition with the respirasomes, which they read as showing that ubiquinone is not channelled and moves freely.⁷

Fedor and Hirst ask why supercomplexes exist if catalysis does not depend on channelling. They cite proposals of lower ROS generation and better stability for complex I, and of protection against aggregation in a protein-dense membrane. They also suggest that supercomplexes may promote quinone diffusion.⁴ For that point they cite simulations of plastoquinone in grana thylakoid membranes, where large obstacles gave higher diffusion rates than small ones.⁴ Sousa and colleagues, by contrast, say the linear arrangement of complexes I, III and IV seems to be particularly favourable for efficient substrate and electron transfer.² Jaeken and Manoj (2025) place ubiquinone among e-buffering molecules in membranes, alongside cytochrome c in water.⁸