{"title":"Knockout of the mitoribosome rescue factors Ict1 or Mtrfr is viable in zebrafish but not mice: compensatory mechanisms underlying each factor's loss.","authors":"Nobukazu Nameki, Chika Tomisawa, Soichiro Hoshino, Hidehiko Shimizu, Masashi Abe, Sho Arai, Kanako Kuwasako, Naoki Asakawa, Yusuke Inoue, Takuro Horii, Izuho Hatada, Masakatsu Watanabe","doi":"10.1002/2211-5463.70054","DOIUrl":null,"url":null,"abstract":"<p><p>The mitochondrial translation system contains two ribosome rescue factors, ICT1 and MTRFR (C12orf65), which hydrolyze peptidyl-tRNA in stalled ribosomes. ICT1 also functions as a ribosomal protein of the mitochondrial large ribosomal subunit (mtLSU) in mice and humans, and its deletion is lethal. In contrast, MTRFR does not share this role. Although loss-of-function mutations in MTRFR have been linked to human mitochondrial diseases, data on this association in other vertebrates are lacking. Here, attempts to generate Mtrfr knockout mice were unsuccessful. However, knockout zebrafish lines were successfully generated for both ict1 and mtrfr (ict1<sup>-/-</sup> and mtrfr<sup>-/-</sup>). Both knockout lines appeared healthy and fertile. ict1<sup>-/-</sup>, mtrfr<sup>-/-</sup>, and wild-type adult caudal fin cells showed significant differences in mitochondrial morphology. The ict1 deletion affected the network properties more than the number of individuals and networks, whereas the mtrfr deletion exhibited the opposite effect. Additionally, the survival rates of the knockout line larvae were significantly lower than those of the wild-type larvae under starvation conditions. These results suggest that ict1 and mtrfr are required for survival under specific stress conditions, whereas ict1<sup>-/-</sup> and mtrfr<sup>-/-</sup> involve different compensatory mechanisms in response to loss of either factor under nonstress conditions. Ict1 proteins from all teleosts, including zebrafish, lack the N-terminal mtLSU-binding motif found in most metazoans, suggesting that Ict1 does not function as a ribosomal protein in teleosts. Thus, Mtrfr may partially compensate for the loss of Ict1. In conclusion, zebrafish appear to exemplify a limited category of vertebrates capable of enduring genetic abnormalities in ict1 or mtrfr.</p>","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Open Bio","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/2211-5463.70054","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The mitochondrial translation system contains two ribosome rescue factors, ICT1 and MTRFR (C12orf65), which hydrolyze peptidyl-tRNA in stalled ribosomes. ICT1 also functions as a ribosomal protein of the mitochondrial large ribosomal subunit (mtLSU) in mice and humans, and its deletion is lethal. In contrast, MTRFR does not share this role. Although loss-of-function mutations in MTRFR have been linked to human mitochondrial diseases, data on this association in other vertebrates are lacking. Here, attempts to generate Mtrfr knockout mice were unsuccessful. However, knockout zebrafish lines were successfully generated for both ict1 and mtrfr (ict1-/- and mtrfr-/-). Both knockout lines appeared healthy and fertile. ict1-/-, mtrfr-/-, and wild-type adult caudal fin cells showed significant differences in mitochondrial morphology. The ict1 deletion affected the network properties more than the number of individuals and networks, whereas the mtrfr deletion exhibited the opposite effect. Additionally, the survival rates of the knockout line larvae were significantly lower than those of the wild-type larvae under starvation conditions. These results suggest that ict1 and mtrfr are required for survival under specific stress conditions, whereas ict1-/- and mtrfr-/- involve different compensatory mechanisms in response to loss of either factor under nonstress conditions. Ict1 proteins from all teleosts, including zebrafish, lack the N-terminal mtLSU-binding motif found in most metazoans, suggesting that Ict1 does not function as a ribosomal protein in teleosts. Thus, Mtrfr may partially compensate for the loss of Ict1. In conclusion, zebrafish appear to exemplify a limited category of vertebrates capable of enduring genetic abnormalities in ict1 or mtrfr.
期刊介绍:
FEBS Open Bio is an online-only open access journal for the rapid publication of research articles in molecular and cellular life sciences in both health and disease. The journal''s peer review process focuses on the technical soundness of papers, leaving the assessment of their impact and importance to the scientific community.
FEBS Open Bio is owned by the Federation of European Biochemical Societies (FEBS), a not-for-profit organization, and is published on behalf of FEBS by FEBS Press and Wiley. Any income from the journal will be used to support scientists through fellowships, courses, travel grants, prizes and other FEBS initiatives.