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Updated: Dec 11, 2025
Author Spotlight: Advancing Techniques and Discoveries in Protein Synthesis and Assembly Through Innovative Mitochondrial Research
Published on: June 7, 2024
Structural basis of mitochondrial translation
Shintaro Aibara1, Vivek Singh1,2, Angelika Modelska3
1Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.
Abstract:
Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 Å resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.
Insights
This study reveals how human mitoribosomes bind mitochondrial messenger RNA (mt-mRNA) and move transfer RNA (mt-tRNA) during translation. Key proteins like LRPPRC-SLIRP and mS39 facilitate mt-mRNA delivery, while mL40, mL48, and mL64 coordinate mt-tRNA movement.
Area of Science:
- Molecular Biology
- Structural Biology
- Mitochondrial Biology
Background:
- Mitochondrial translation relies on specialized mitoribosomes with unique proteins.
- The precise roles of these proteins in messenger RNA (mRNA) binding and transfer RNA (tRNA) translocation remain largely unknown.
Purpose of the Study:
- To elucidate the structural mechanisms of human mitochondrial translation.
- To visualize the interactions between mitoribosomes, mRNA, tRNA, and associated factors.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine the structure of the human mitoribosome.
- Multiple structures of functional complexes were resolved at approximately 3.0 Å resolution.
Main Results:
- A protein module (LRPPRC-SLIRP) delivers mitochondrial mRNA (mt-mRNA) to the small ribosomal subunit via a platform formed by mS39.
- Mitoribosomal proteins mL40, mL48, and mL64 are crucial for coordinating mitochondrial tRNA (mt-tRNA) translocation.
- Dynamic interactions and sequential conformational changes were observed during translation.
Conclusions:
- The study provides a detailed structural basis for human mitochondrial translation.
- Identifies specific protein players and mechanisms involved in mt-mRNA binding and mt-tRNA translocation.
- Reveals a dynamic, stepwise process governing mitochondrial protein synthesis.
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