{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have implicated a conserved nuclear protein, Kin17, in safeguarding genomic integrity. Kin17 is up-regulated in response to genotoxic stress, where it binds DNA and RNA—including a preference for poly(G) and poly(U) sequences—and is integrated into the spliceosome, hinting at important roles in RNA processing and nuclear metabolism. In addition, Kin17 is essential for the timely repair of DNA double-stranded breaks that arise either from endogenous (activation‐induced deaminase) or exogenous (ionizing radiation) insults, with reduced Kin17 function leading to elevated deletion frequencies during class switch recombination in B cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, investigations into the Von Willebrand A domain-containing protein 8 (VWA8) have revealed its localization to mitochondria and its classification as an AAA ATPase. VWA8 exists in at least two splice variants—a full-length version and a truncated isoform—and harbors a mitochondrial targeting sequence necessary for its exclusive mitochondrial localization. Biochemical studies demonstrate that VWA8 possesses ATPase activity that is critically dependent on its Walker A and Walker B motifs, and its expression is elevated in tissues such as liver in response to high-fat feeding."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional ablation of VWA8 in hepatocytes provokes a cascade of compensatory changes, including increased mitochondrial and peroxisomal oxidative capacity, heightened reactive oxygen species production, and an up-regulation of hepatocyte nuclear factor 4α. This evidence supports the notion that VWA8 plays a key role in mitochondrial protein quality control and metabolic homeostasis, with its loss triggering responses aimed at counteracting oxidative stress. Together, these studies underscore a dual cellular strategy wherein nuclear factors such as Kin17 ensure genomic and RNA integrity, while mitochondrial regulators like VWA8 maintain bioenergetic and proteostatic balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ghislaine Pinon-Lataillade, Christel Masson, Jacqueline Bernardino-Sgherri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KIN17 encodes an RNA-binding protein and is expressed during mouse spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.01226"}], "href": "https://doi.org/10.1242/jcs.01226"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15252136"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15252136"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Michael X Le, Dania Haddad, Alexanda K Ling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kin17 facilitates multiple double-strand break repair pathways that govern B cell class switching."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep37215"}], "href": "https://doi.org/10.1038/srep37215"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27853268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27853268"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Moulun Luo, April E Mengos, Wuqiong Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the novel protein KIAA0564 (Von Willebrand Domain-containing Protein 8)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.04.067"}], "href": "https://doi.org/10.1016/j.bbrc.2017.04.067"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28414126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28414126"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Brian S Grewe, Janet E Richmond, David E Featherstone "}, {"type": "b", "children": [{"type": "t", "text": "The spatial and developmental expression of mouse Vwa8 (von Willebrand domain-containing protein 8)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene Expr Patterns (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gep.2018.04.004"}], "href": "https://doi.org/10.1016/j.gep.2018.04.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29660410"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29660410"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Moulun Luo, Wayne T Willis, Dawn K Coletta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deletion of the Mitochondrial Protein VWA8 Induces Oxidative Stress and an HNF4α Compensatory Response in Hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.biochem.9b00863"}], "href": "https://doi.org/10.1021/acs.biochem.9b00863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31702900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31702900"}]}]}]}