{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUQCC3, encoded by the C11orf83 gene, is a mitochondrial inner membrane protein that serves as an essential assembly factor for Complex III (cytochrome bc₁ complex) of the electron transport chain. In one study, a homozygous missense mutation in UQCC3 was linked to reduced Complex III activity, diminished levels of cytochrome b, and defective assembly of the high-molecular-weight Complex III, underscoring its critical role downstream of other assembly factors UQCC1 and UQCC2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have demonstrated that UQCC3 closely associates with the bc₁ core and binds cardiolipin via specific α-helices, thereby contributing to the stabilization of Complex III-containing supercomplexes (notably the dimeric Complex III and its association with Complex IV). Loss of UQCC3 leads to abnormal mitochondrial crista morphology, impaired ATP production due to defective respiration, and increased cellular sensitivity to apoptotic stimuli."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its structural role in mitochondrial electron transport, UQCC3 has been implicated in innate antiviral defense. In response to viral infection, UQCC3 expression increases and enhances the transcription of antiviral effectors such as OAS3, thereby promoting the activation of the RNase L pathway. This antiviral mechanism operates independently of interferon production, suggesting that UQCC3 bridges mitochondrial metabolic components with cellular antiviral effectors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, under hypoxic conditions, UQCC3 expression is markedly upregulated and correlates with poor clinical outcomes in hepatocellular carcinoma. In this context, UQCC3 participates in a positive feedback loop with mitochondrial reactive oxygen species (ROS), which not only sustains its own expression but also helps preserve mitochondrial structure and function. This, in turn, stabilizes HIF‑1α, enhancing glycolysis and promoting tumor cell proliferation during hypoxia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bas F J Wanschers, Radek Szklarczyk, Mariël A M van den Brand, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A mutation in the human CBP4 ortholog UQCC3 impairs complex III assembly, activity and cytochrome b stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu357"}], "href": "https://doi.org/10.1093/hmg/ddu357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25008109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25008109"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marjorie Desmurs, Michelangelo Foti, Etienne Raemy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex assembly and supercomplex stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01047-14"}], "href": "https://doi.org/10.1128/MCB.01047-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25605331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25605331"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yun Yang, Shaoquan Xiong, Bei Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial C11orf83 is a potent Antiviral Protein Independent of interferon production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep44303"}], "href": "https://doi.org/10.1038/srep44303"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28418037"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28418037"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yun Yang, Guimin Zhang, Fengzhu Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial UQCC3 Modulates Hypoxia Adaptation by Orchestrating OXPHOS and Glycolysis in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2020.108340"}], "href": "https://doi.org/10.1016/j.celrep.2020.108340"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33147459"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33147459"}]}]}]}