Rieske iron-sulfur domain mobility and electron transfer in complex III
The Rieske protein is a subunit of complex III, the bc1 complex. Its iron-sulfur domain carries electrons from the quinol site, through an iron-sulfur cluster, to heme c1. Soluble cytochrome c then takes them on to complex IV. The domain does this by moving on a hinge, and when the movement is blocked, no electrons reach cytochrome c1.12
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- 2016, Sousa JS, Mills DJ, Vonck J…
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- Functional asymmetry and electron flow in the…, 2016
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- 2026-10-29
Place in the Q-cycle
Protasoni and Zeviani (2021) describe complex III as the enzyme that oxidizes quinol and passes electrons to cytochrome c in the Q-cycle. The cycle involves the heme groups of cytochrome c1 and cytochrome b and the 2Fe/2S cluster of the Rieske protein, also called UQCRFS1.7 In their account, one electron from quinol bound at the Qo site goes to the iron-sulfur group, then to cytochrome c1, and so to cytochrome c. The second electron goes to the b hemes.7 They also report that recent studies proposed that the N-terminal UQCRFS1 peptide needs to be eliminated to maintain complex III functionality.8
The hinge and its positions
Sousa and colleagues (2016) cite Iwata and co-workers (1998) for a hinge motion of 10 to 15 Å that brings the domain to cytochrome c1.1 They cite Darrouzet and co-workers (2000) for the finding that blocking this motion stops electron transfer to cytochrome c1.2 Brzezinski, Moe and Ädelroth (2021) describe crystal structures with two extreme positions, one near cytochrome c1 (C) and one near heme bL (B). They give the distance between them as almost 20 Å. Structural data suggested the cluster accepts electrons from quinol only in B.5 They add that the link between quinol binding, the redox state of the cluster and the balance between the two positions remains enigmatic.6
Asymmetry in the respirasome
Sousa and colleagues (2016) found an unexpected feature in their bovine respirasome map. Only one of the two iron-sulfur domains of the complex III dimer showed clear density. They noted that a domain moving 10 to 15 Å would be invisible in a 9 Å map.1 The domain that bridges the electron path within one monomer belongs to the Rieske protein of the other monomer.3 They contrast this with the porcine and ovine respirasome structures, where both domains are resolved. They conclude that neither of those structures shows a mobile, catalytically active Rieske protein.4 They report that Letts and colleagues proposed that complex IV's proximity to the outer monomer prevents the outer iron-sulfur domain's movement. Sousa and colleagues add that neither structure shows direct contacts that would inhibit it.4
Handing on to cytochrome c
The electron path ends at cytochrome c1, where cytochrome c collects it. Morse and colleagues (2024) report that lysine 8 of cytochrome c interacts with cytochrome c1. An acetylmimetic K8Q form of cytochrome c had a perturbed dissociation constant from cytochrome c1.9 The same residue also contacts complex IV. They say little is known about what this modification does to the other functions of cytochrome c.9
In order to transfer electrons to c1, the iron-sulfur domain has to move on a hinge by 10–15 Å (Iwata et al., 1998).
Sousa JS, Mills DJ, Vonck J, Kühlbrandt W, 2016 · Functional asymmetry and electron flow in the bovine respirasome · open at passage 19The hinge movement of the iron-sulfur domain is essential for function since when it is blocked, no electrons are transferred to cytochrome c1 (Darrouzet et al., 2000).
Sousa JS, Mills DJ, Vonck J, Kühlbrandt W, 2016 · Functional asymmetry and electron flow in the bovine respirasome · open at passage 19Interestingly, the iron-sulfur domain that bridges the gap in the electron transfer path between the hemes of one complex III monomer belongs to the Rieske protein of the opposite monomer.
Sousa JS, Mills DJ, Vonck J, Kühlbrandt W, 2016 · Functional asymmetry and electron flow in the bovine respirasome · open at passage 19Surprisingly, the two iron-sulfur domains in the complex III dimer are both resolved in the porcine and ovine respirasome, whereas one of them is disordered in our structure of the bovine complex.
Sousa JS, Mills DJ, Vonck J, Kühlbrandt W, 2016 · Functional asymmetry and electron flow in the bovine respirasome · open at passage 30The distance spanned by the FeS cluster while moving between the B and C positions is almost 20 Å, and the structural data suggested that the FeS cluster could accept electrons from QH2 (in site QP) only in the B position
Brzezinski P, Moe A, Ädelroth P, 2021 · Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic… · open at passage 17However, the link between Q/QH2 binding in the QP site, the redox state of FeS and the equilibrium constant for the two FeS-domain positions remains enigmatic.
Brzezinski P, Moe A, Ädelroth P, 2021 · Structure and Mechanism of Respiratory III-IV Supercomplexes in Bioenergetic… · open at passage 17The first reaction requires the passage of one electron from QH2 bound to the Qo binding site to the iron/sulfur group and then to cytochrome c1, leading to the reduction of cytochrome c.
Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 46However, recent studies proposed that the latter is not a stoichiometric subunit and that the N-terminal UQCRFS1 peptide needs to be eliminated in order to maintain the functionality of CIII
Protasoni M, Zeviani M, 2021 · Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions · open at passage 62This residue is known to interact with cytochrome c1 of Complex III [99,100], and it was found that acetylmimetic K8Q Cytc had a perturbed dissociation constant from cytochrome c1 [98].
Morse PT, Arroum T, Wan J, Pham L, Vaishnav A, Bell J…, 2024 · Phosphorylations and Acetylations of Cytochrome c Control Mitochondrial… · open at passage 36