RESUMO
Mitochondrial gene expression relies on mitoribosomes to translate mitochondrial mRNAs. The biogenesis of mitoribosomes is an intricate process involving multiple assembly factors. Among these factors, GTP-binding proteins (GTPBPs) play important roles. In bacterial systems, numerous GTPBPs are required for ribosome subunit maturation, with EngB being a GTPBP involved in the ribosomal large subunit assembly. In this study, we focus on exploring the function of GTPBP8, the human homolog of EngB. We find that ablation of GTPBP8 leads to the inhibition of mitochondrial translation, resulting in significant impairment of oxidative phosphorylation. Structural analysis of mitoribosomes from GTPBP8 knock-out cells shows the accumulation of mitoribosomal large subunit assembly intermediates that are incapable of forming functional monosomes. Furthermore, fPAR-CLIP analysis reveals that GTPBP8 is an RNA-binding protein that interacts specifically with the mitochondrial ribosome large subunit 16 S rRNA. Our study highlights the role of GTPBP8 as a component of the mitochondrial gene expression machinery involved in mitochondrial large subunit maturation.
Assuntos
Proteínas de Ligação ao GTP , Mitocôndrias , Ribossomos Mitocondriais , Fosforilação Oxidativa , Humanos , Ribossomos Mitocondriais/metabolismo , Mitocôndrias/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/genética , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Células HEK293 , Biossíntese de Proteínas , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Células HeLaRESUMO
New nickel(ii), palladium(ii), and platinum(iv) complexes were synthesized by reacting the metal ions with benzidinedioxime in a 1 : 1 mole ratio. The CHN elemental analysis, spectroscopic analyses, and powder X-ray diffraction (PXRD) results showed that two Ni(ii) and two Pd(ii) ions coordinated to two benzidinedioxime ligands via the nitrogen atoms of both oxime groups and the two azomethine nitrogen atoms. In the case of the dinuclear platinum(iv) complex, however, each Pt(iv) is coordinated with the two oxygen atoms of the oxime group and the two azomethine nitrogen atoms of the ligand. Both elemental analyses and PXRD indicated that the complex ions of Ni(ii) and Pt(iv) have distorted octahedral geometry, whereas Pd(ii) has a square planar geometry. Molecular docking studies showed that the nickel(ii) complex is the most potent dual DHPS/DHFR bacterial inhibitor. The receptor of the DHPS enzyme (3ZTE) showed the best interaction with the nickel(ii) complex when compared to a receptor of the DHFR enzyme (3FRB). All the synthesized complexes and ligand exhibited significant results against PS. Aeruginous than their corresponding SMX-TMP drug. Among the three synthesized complexes, the nickel(ii) complex possessed the highest antimicrobial activities against tested microorganisms.