Reactome | Electron transfer from reduced cytochrome c to molecular oxygen

Electron transfer from reduced cytochrome c to molecular oxygen

Stable Identifier

R-HSA-163214

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial inner membrane, mitochondrial intermembrane space, mitochondrial matrix

ReviewStatus

5/5

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Electron transfer from reduced cytochrome c to molecular oxygen

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Complex IV (COX, cytochrome c oxidase) contains the hemeprotein cytochrome a and a3. It also contains copper atoms which undergo a transition from Cu+ to Cu2+ during the transfer of electrons through the complex to molecular oxygen. A bimetallic center containing a copper atom and a heme-linked iron protein binds oxygen after 4 electrons have been picked up. Water, the final product of oxygen reduction, is then released. Oxygen is the final electron acceptor in the respiratory chain. The overall reaction can be summed as

4Cyt c (red.) + 12H+ (in) + O2 = 4Cyt c (ox.) + 2H2O + 8H+ (out)

Four protons are taken up from the matrix side of the membrane to form the water (scalar protons). Wikstrom (1977) suggests 4 protons are additionally transferred out from the matrix to the intermembrane space.

Carbon monoxide (CO) readily inhibits oxygen consumption by mitochondrial cytochrome oxidase. This inhibition is responsible for much of its toxicity when it is applied externally to the body. However, CO has been implicated in normal cellular signaling, especially in anti-inflammatory effects. The addition of antioxidants or inhibition of complex III of the electron transport chain by antimycin A attenuates the inhibitory effects of CO on lipopolysaccharide (LPS)-induced NLRP3 formation and TNF-alpha secretion, and blocked CO-induced p38 MAPK phosphorylation. These effects may be mediated via inhibition of cytochrome c oxidase and its generation of mitochondrial reactive oxygen species (Alonso et al, 2003; Zuckerbraun et al, 2007; Cooper and Brown, 2008; Jung et al, 2014; Ishigami et al, 2017). In carotid body glomus cells the tissue-specific HIGD1C positively regulates COX electron transfer (Timón-Gómez et al., 2022).

Literature References

PubMed ID	Title	Journal	Year
11340051	Structures and proton-pumping strategies of mitochondrial respiratory Schultz, BE, Chan, SI	Annu Rev Biophys Biomol Struct	2001
16760263	Assembly of mitochondrial cytochrome c-oxidase, a complicated and highly regulated cellular process Fontanesi, F, Soto, IC, Horn, D, Barrientos, A	Am. J. Physiol., Cell Physiol.	2006
36255054	Tissue-specific mitochondrial HIGD1C promotes oxygen sensitivity in carotid body chemoreceptors Timón-Gómez, A, Scharr, AL, Wong, NY, Ni, E, Roy, A, Liu, M, Chau, J, Lampert, JL, Hireed, H, Kim, NS, Jan, M, Gupta, AR, Day, RW, Gardner, JM, Wilson, RJA, Barrientos, A, Chang, AJ	Elife	2022
15223	Proton pump coupled to cytochrome c oxidase in mitochondria Wikstrom, MK	Nature	1977
7979252	Energy transduction by cytochrome complexes in mitochondrial and bacterial Trumpower, BL, Gennis, RB	Annu Rev Biochem	1994
17298220	Biogenesis of eukaryotic cytochrome c oxidase Stiburek, L, Hansikova, H, Tesarova, M, Cerna, L, Zeman, J	Physiol Res	2006
21958598	Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic core Soto, IC, Fontanesi, F, Liu, J, Barrientos, A	Biochim. Biophys. Acta	2012