Distinct Mechanisms of the Human Mitoribosome Recycling and Antibiotic Resistance

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jun 15

PMID 34127662

Citations 8

Authors

Ravi Kiran Koripella

Ayush Deep

Ekansh K Agrawal

Pooja Keshavan

Nilesh K Banavali

Rajendra K Agrawal

Affiliations

Soon will be listed here.

Abstract

Ribosomes are recycled for a new round of translation initiation by dissociation of ribosomal subunits, messenger RNA and transfer RNA from their translational post-termination complex. Here we present cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) and the mitoribosomal large 39S subunit in complex with mitoribosome recycling factor (RRF) and a recycling-specific homolog of elongation factor G (EF-G2). These structures clarify an unusual role of a mitochondria-specific segment of RRF, identify the structural distinctions that confer functional specificity to EF-G2, and show that the deacylated tRNA remains with the dissociated 39S subunit, suggesting a distinct sequence of events in mitoribosome recycling. Furthermore, biochemical and structural analyses reveal that the molecular mechanism of antibiotic fusidic acid resistance for EF-G2 is markedly different from that of mitochondrial elongation factor EF-G1, suggesting that the two human EF-Gs have evolved diversely to negate the effect of a bacterial antibiotic.

Citing Articles

Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics.

Bibel B, Raskar T, Couvillion M, Lee M, Kleinman J, Takeuchi-Tomita N Nucleic Acids Res. 2025; 53(3).

PMID: 39907106 PMC: 11795202. DOI: 10.1093/nar/gkaf046.

Selection of initiator tRNA and start codon by mammalian mitochondrial initiation factor 3 in leaderless mRNA translation.

Lee M, Wakigawa T, Jia Q, Liu C, Huang R, Huang S Nucleic Acids Res. 2025; 53(3).

PMID: 39878211 PMC: 11775629. DOI: 10.1093/nar/gkaf021.

Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics.

Bibel B, Raskar T, Couvillion M, Lee M, Kleinman J, Takeuchi-Tomita N bioRxiv. 2024; .

PMID: 39229136 PMC: 11370408. DOI: 10.1101/2024.08.21.609012.

The human mitochondrial translation factor TACO1 alleviates mitoribosome stalling at polyproline stretches.

Brischigliaro M, Kruger A, Moran J, Antonicka H, Ahn A, Shoubridge E Nucleic Acids Res. 2024; 52(16):9710-9726.

PMID: 39036954 PMC: 11381339. DOI: 10.1093/nar/gkae645.

Time resolution in cryo-EM using a PDMS-based microfluidic chip assembly and its application to the study of HflX-mediated ribosome recycling.

Bhattacharjee S, Feng X, Maji S, Dadhwal P, Zhang Z, Brown Z Cell. 2024; 187(3):782-796.e23.

PMID: 38244547 PMC: 10872292. DOI: 10.1016/j.cell.2023.12.027.

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