{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytochrome c oxidase subunit II (commonly referred to as COX2) is a pivotal component of Complex IV in the mitochondrial electron transport chain, where it drives the final electron transfer step essential for ATP production. Recent findings extend its role beyond bioenergetics to the regulation of cell survival and apoptotic signaling. For example, activation of the epidermal growth factor receptor (EGFR) by its ligand leads to EGFR translocation to the mitochondria where, upon phosphorylation of a specific tyrosine residue (Y845), EGFR directly binds COX2. This interaction is critical for modulating mitochondrial function and enhancing survival pathways by delaying apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, the proper synthesis and assembly of COX2 is tightly regulated by mitochondrial metallochaperones. SCO2 functions as a thiol–disulphide oxidoreductase that modifies SCO1—its partner in the maturation process—thereby ensuring the insertion of essential copper ions into COX2 during its biogenesis. Disruption of this redox-regulated assembly process impairs COX2 synthesis and compromises mitochondrial respiration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, mutations in genes such as LRPPRC can lead to reduced stability of mitochondrial mRNAs encoding COX subunits. This reduction predominantly affects COX2 levels, resulting in defective cytochrome c oxidase assembly and diminished electron transport function, as observed in certain neurodegenerative syndromes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight that COX2 is not only essential for efficient oxidative phosphorylation but is also integrated into complex signaling networks that control mitochondrial integrity and programmed cell death. Its regulation via post‐translational interactions and precise assembly mechanisms underscores its multifaceted role in cellular metabolism and survival (1,2,3).\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julie L Boerner, Michelle L Demory, Corinne Silva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.16.7059-7071.2004"}], "href": "https://doi.org/10.1128/MCB.24.16.7059-7071.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15282306"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15282306"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Scot C Leary, Florin Sasarman, Tamiko Nishimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human SCO2 is required for the synthesis of CO II and as a thiol-disulphide oxidoreductase for SCO1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp158"}], "href": "https://doi.org/10.1093/hmg/ddp158"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19336478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19336478"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Florin Sasarman, Catherine Brunel-Guitton, Hana Antonicka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e10-01-0047"}], "href": "https://doi.org/10.1091/mbc.e10-01-0047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20200222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20200222"}]}]}]}