Abstract

Mitochondria contain a multi-copy genome and a distinct set of ribosomes devoted to the exclusive synthesis of proteins that are essential for oxidative phosphorylation. The assembly of mitoribosomes for mitochondrial translation is a poorly understood process. In this study, we identify the uncharacterized GTP-binding protein 8 (GTPBP8) as a mitoribosomal assembly factor that specifically associates with the mitoribosomal large subunit. Genetic depletion of GTPBP8 causes an aberrant accumulation of the large mitoribosomal subunit at a late assembly stage and reduces the level of fully assembled 55S mitoribosomes, resulting in impaired mitochondrial translation and function. Together, our findings uncover an important role for human GTPBP8 in the processes of mitoribosomal assembly and mitochondrial translation. Key pointsO_LIGTPBP8 is a novel GTPase residing in the matrix peripherally bound to the inner mitochondrial membrane C_LIO_LIGTPBP8 specifically associates with the large mitoribosome subunit through interactions with large mitoribosomal proteins assembled at late stages. C_LIO_LIGTPBP is essential for maturation of the mitoribosomal large subunit and monosome formation C_LI