Document Type

Article

Version Deposited

Published Version

Publication Date

6-21-2019

Publication Title

The Journal of Biological Chemistry

DOI

10.1074/jbc.RA119.008476

Abstract

Mitochondrial ribosomes are functionally specialized for the synthesis of several essential inner membrane proteins of the respiratory chain. Although remarkable progress has been made toward understanding the structure of mitoribosomes, the pathways and factors that facilitate their biogenesis remain largely unknown. The long unstructured domains of unassembled ribosomal proteins are highly prone to misfolding and often require dedicated chaperones to prevent aggregation. To date, chaperones that ensure safe delivery to the assembling ribosome have not been identified in the mitochondrion. In this study, a respiratory synthetic lethality screen revealed a role for an evolutionarily conserved mitochondrial matrix protein called Mam33 in Saccharomyces cerevisiae mitoribosome biogenesis. We found that the absence of Mam33 results in misassembled, aggregated ribosomes and a respiratory lethal phenotype in combination with other ribosome-assembly mutants. Using sucrose gradient sedimentation, native affinity purifications, in vitro binding assays, and SILAC-based quantitative proteomics, we found that Mam33 does not associate with the mature mitoribosome, but directly binds a subset of unassembled large subunit proteins. Based on these data, we propose that Mam33 binds specific mitoribosomal proteins to ensure proper assembly.

Comments

“Authors are allowed…to post the final edited PDFs, created by ASBMB, to their own departmental/university websites, provided that the posting does not happen until 12 months after publication of the work, and that a link to the article on the journal site is included.”

Published Citation

Hillman GA, Henry MF. The yeast protein Mam33 functions in the assembly of the mitochondrial ribosome. Journal of Biological Chemistry. 2019 Jun 21;294(25):9813-9829. Epub 2019 May 3. doi: 10.1074/jbc.RA119.008476. PMID: 31053642. PMCID: PMC6597815.

Available for download on Monday, June 22, 2020

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