Document Type
Article
Publication Date
2024
Publisher
American Society for Biochemistry and Molecular Biology
Source Publication
Journal of Biological Chemistry
Source ISSN
0021-9258
Original Item ID
DOI: 10.1016/j.jbc.2024.107519
Abstract
The mitochondrial ribosome (mitoribosome) is responsible for the synthesis of key oxidative phosphorylation subunits encoded by the mitochondrial genome. Defects in mitoribosomal function therefore can have serious consequences for the bioenergetic capacity of the cell. Mutation of the conserved mitoribosomal mL44 protein has been directly linked to childhood cardiomyopathy and progressive neurophysiology issues. To further explore the functional significance of the mL44 protein in supporting mitochondrial protein synthesis, we have performed a mutagenesis study of the yeast mL44 homolog, the MrpL3/mL44 protein. We specifically investigated the conserved hydrophobic pocket region of the MrpL3/mL44 protein, where the known disease-related residue in the human mL44 protein (L156R) is located. While our findings identify a number of residues in this region critical for MrpL3/mL44’s ability to support the assembly of translationally active mitoribosomes, the introduction of the disease-related mutation into the equivalent position in the yeast protein (residue A186) was found to not have a major impact on function. The human and yeast mL44 proteins share many similarities in sequence and structure; however results presented here indicate that these two proteins have diverged somewhat in evolution. Finally, we observed that mutation of the MrpL3/mL44 does not impact the translation of all mitochondrial encoded proteins equally, suggesting the mitochondrial translation system may exhibit a transcript hierarchy and prioritization.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Box, Jodie M.; Higgins, Margo E.; and Stuart, Rosemary A., "Importance of Conserved Hydrophobic Pocket Region in Yeast Mitoribosomal mL44 Protein for Mitotranslation and Transcript Preference" (2024). Biological Sciences Faculty Research and Publications. 998.
https://epublications.marquette.edu/bio_fac/998
Comments
Published version. Journal of Biological Chemistry, Vol. 300, No. 8 (2024). DOI. © 2024 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. Used with permission.