GTPBP8 is required for mitoribosomal biogenesis and mitochondrial translation

• Published in: Cellular and molecular life sciences : CMLS 2023-12, Vol.80 (12), p.361-361, Article 361
• Main Authors: Wang, Liang, Hilander, Taru, Liu, Xiaonan, Tsang, Hoi Ying, Eriksson, Ove, Jackson, Christopher B., Varjosalo, Markku, Zhao, Hongxia
• Format: Article
• Language: English
• Subjects: Assembly; Biochemistry; biogenesis; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cell Biology; Chemical synthesis; GTP-binding protein; GTP-Binding Proteins - genetics; GTP-Binding Proteins - metabolism; guanosinetriphosphatase; Life Sciences; Mitochondria; Mitochondria - metabolism; mitochondrial membrane; Mitochondrial Membranes - metabolism; mitochondrial proteins; Mitochondrial Proteins - metabolism; Mitochondrial Ribosomes - chemistry; Mitochondrial Ribosomes - metabolism; Molecular modelling; Original Article; Protein Biosynthesis; Protein synthesis; Proteins; Ribonucleic acid; Ribosomal Proteins - genetics; Ribosomal Proteins - metabolism; ribosomes; RNA; Translation; Yeast
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-023-05014-0

Mitochondrial translation occurs on the mitochondrial ribosome, also known as the mitoribosome. The assembly of mitoribosomes is a highly coordinated process. During mitoribosome biogenesis, various assembly factors transiently associate with the nascent ribosome, facilitating the accurate and efficient construction of the mitoribosome. However, the specific factors involved in the assembly process, the precise mechanisms, and the cellular compartments involved in this vital process are not yet fully understood. In this study, we discovered a crucial role for GTP-binding protein 8 (GTPBP8) in the assembly of the mitoribosomal large subunit (mt-LSU) and mitochondrial translation. GTPBP8 is identified as a novel GTPase located in the matrix and peripherally bound to the inner mitochondrial membrane. Importantly, GTPBP8 is specifically associated with the mt-LSU during its assembly. Depletion of GTPBP8 leads to an abnormal accumulation of mt-LSU, indicating that GTPBP8 is critical for proper mt-LSU assembly. Furthermore, the absence of GTPBP8 results in reduced levels of fully assembled 55S monosomes. This impaired assembly leads to compromised mitochondrial translation and, consequently, impaired mitochondrial function. The identification of GTPBP8 as an important player in these processes provides new insights into the molecular mechanisms underlying mitochondrial protein synthesis and its regulation.