Recombinant Mouse Cytochrome c oxidase subunit 4 isoform 1, mitochondrial (Cox4i1), partial

Function

Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix

Subcellular Location

Mitochondrion inner membrane (Single-pass membrane protein)

Subunit

Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits (PubMed:34616041, PubMed:38575788). The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and COXFA4, which are encoded in the nuclear genome (PubMed:34616041, PubMed:38575788). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:34616041, PubMed:38575788). Interacts with PHB2; the interaction decreases in absence of SPHK2 (PubMed:20959514). Interacts with AFG1L (By similarity). Interacts with ABCB7; this interaction allows the regulation of cellular iron homeostasis and cellular reactive oxygen species (ROS) levels in cardiomyocytes (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and is disrupted upon heme binding (PubMed:32973183). Interacts with IRGC (PubMed:37195149)

Pathway

Energy metabolism; oxidative phosphorylation

• Grossman L.I. et al. Nucleotide sequence of a mouse cDNA for subunit IV of cytochrome c oxidase. — Nucleic Acids Res. (1990)
• Carter R.S. et al. Cloning and characterization of the mouse cytochrome c oxidase subunit IV gene. — Arch. Biochem. Biophys. (1991)
• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• Lubec G. et al. PubMed: CI-92NG82E19BM4T (APR-)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Strub G.M. et al. Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. — FASEB J. (2011)
• Park J. et al. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. — Mol. Cell (2013)
• Rardin M.J. et al. Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways. — Proc. Natl. Acad. Sci. U.S.A. (2013)