{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have identified UQCC6—also known as BRAWNIN, a 71–amino acid mitochondrial peptide encoded by C12orf73—as a pivotal factor in the assembly of respiratory chain complex III. UQCC6 is localized in the mitochondrial membrane and is essential for proper oxidative phosphorylation, ensuring efficient ATP production. Disruption of its expression leads to impaired complex III assembly and mitochondrial dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn human cells, UQCC6 is responsive to cellular energy status; its expression is modulated by energy-sensing pathways such as AMPK. Nutritional stress appears to induce UQCC6, which in turn supports mitochondrial function by stabilizing complex III assembly. Notably, while complete deletion of UQCC6 severely disrupts complex III formation and mitochondrial ATP production, even minimal presence—as observed in knockdown experiments—can suffice for maintaining oxidative phosphorylation, although subtle shifts in pyruvate metabolism may occur."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, in vivo investigations using zebrafish models have underscored the crucial role of UQCC6. Its complete loss results in the total absence of complex III, triggering severe growth retardation, lactic acidosis, and early mortality. These findings not only emphasize the indispensable role of UQCC6 in vertebrate mitochondrial bioenergetics but also highlight its potential function in fine‐tuning mitochondrial metabolic routes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shan Zhang, Boris Reljić, Chao Liang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-14999-2"}], "href": "https://doi.org/10.1038/s41467-020-14999-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32161263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32161263"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ya Wang, Yu Shi, Wen Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of BRAWNIN minimally affect mitochondrial complex III assembly in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2023.119601"}], "href": "https://doi.org/10.1016/j.bbamcr.2023.119601"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37769950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37769950"}]}]}]}