Located in the central protuberance region of the mitoribosome and mitospecific mL38 proteins display homology to PEBP (Phosphatidylethanolamine Binding Protein) proteins, a diverse family of proteins reported to bind anionic substrates/ligands and implicated in cellular signaling and differentiation pathways. In this study, we have performed a mutational analysis of the yeast mitoribosomal protein MrpL35/mL38 and demonstrate that mutation of the PEBP-invariant ligand binding residues Asp(D)232 and Arg(R)288 impacted MrpL35/mL38’s ability to support OXPHOS-based growth of the cell. Furthermore, our data indicate these residues exist in a functionally important charged microenvironment, which also includes Asp(D)167 of MrpL35/mL38 and Arg(R)127 of the neighboring Mrp7/bL27m protein. We report that mutation of each of these charged residues resulted in a strong reduction in OXPHOS complex levels that was not attributed to a corresponding inhibition of the mitochondrial translation process. Rather, our findings indicate that a disconnect exists in these mutants between the processes of mitochondrial protein translation and the events required to ensure the competency and/or availability of the newly synthesized proteins to assemble into OXPHOS enzymes. Based on our findings, we postulate that the PEBP-homology domain of MrpL35/mL38, together with its partner Mrp7/bL27m, form a key regulatory region of the mitoribosome.
- Award ID(s):
- 1817682
- NSF-PAR ID:
- 10332784
- Editor(s):
- Glick, Benjamin
- Date Published:
- Journal Name:
- Molecular Biology of the Cell
- Volume:
- 33
- Issue:
- 1
- ISSN:
- 1059-1524
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1091/mbc.E21-07-0370
