| 描述信息 |
Mitochondrial rRNA modifications are crucial for the assembly and function of mitoribosomes. The m4C methyltransferase METTL15 helps maintain mitochondrial homeostasis by catalyzing the m4C839 modification in 12 S rRNA helix 44. This modification is important for fine-tuning the ribosomal decoding center and enhancing decoding fidelity, as shown in studies with Escherichia coli. We present crystal structures of human METTL15 complexes, including METTL15/hsRBFA/h44/SAM, METTL15/hsRBFA/SAM, METTL15/SAM, and apo METTL15. These structures reveal specific interactions of METTL15 with different substrates and demonstrate that hsRBFA recruits METTL15 to the mitochondrial small subunit for further modifications. Additionally, METTL15 deficiency leads to increased reactive oxygen species, decreased membrane potential, and altered cellular metabolism. Knocking down METTL15 elevates lactate secretion and increases histone lactylation levels (H4K12 and H3K9). METTL15 could serve as a model for studying the link between mitochondrial metabolism and histone lactylation. |
