Structural basis of translation termination, rescue, and recycling in mammalian mitochondria

Kummer, Eva; Schubert, Katharina; Schoenhut, T.; Scaiola, Alain; Ban, Nenad

doi:10.1016/j.molcel.2021.03.042

Cited by 43 publications

(80 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent structural data of mtRF1a bound to mitoribosomes programmed with either UAG- or UAA-containing mRNAs confirmed the role of mtRF1a in translation termination upon recognition of standard stop codons ( Figure 1 , Table 1 ) [ 47 ]. Interactions observed between bacterial RF1, the ribosome and the mRNA are highly conserved in the mtRF1a complex [ 55 ].…”

Section: The Mitochondrial Translation Cyclementioning

confidence: 87%

“…Which of the two codon-specific release factors is the main mitochondrial release factor was, for a long time, an outstanding question. Although mtRF1 was identified as the first mammalian mitochondrial release factors decades ago [ 65 , 66 ], an increasing body of evidence supported the role of mtRF1a as the canonical release factor in mitochondria [ 47 , 64 , 67–70 ].…”

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

“…Huynen and co-workers suggested that mtRF1 might instead be involved in ribosome rescue by binding ribosomes with an empty A site lacking mRNA as it would otherwise sterically clash with a stop codon accommodated in the ribosomal A site. However, a recent structural attempt failed to recover mitoribosomes with mtRF1 bound in positions supporting any of these scenarios, leaving the question of its role in translation termination still open [ 47 ].…”

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

“…A study by Koripella et al (2021) [ 46 ] suggested the extension to be important for stabilizing the rotated conformation of the 55S complex, precluding mtEFG2 binding. However, in a parallel study by Kummer et al (2021) [ 47 ], an N-terminally truncated isoform of mtRRF was used and the recycling efficiency was unaffected.…”

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

See 3 more Smart Citations

Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors

Nadler¹,

Lavdovskaia

Richter‐Dennerlein

2021

RNA Biology

View full text Add to dashboard Cite

The universally conserved process of protein biosynthesis is crucial for maintaining cellular homoeostasis and in eukaryotes, mitochondrial translation is essential for aerobic energy production. Mitochondrial ribosomes (mitoribosomes) are highly specialized to synthesize 13 core subunits of the oxidative phosphorylation (OXPHOS) complexes. Although the mitochondrial translation machinery traces its origin from a bacterial ancestor, it has acquired substantial differences within this endosymbiotic environment. The cycle of mitoribosome function proceeds through the conserved canonical steps of initiation, elongation, termination and mitoribosome recycling. However, when mitoribosomes operate in the context of limited translation factors or on aberrant mRNAs, they can become stalled and activation of rescue mechanisms is required. This review summarizes recent advances in the understanding of protein biosynthesis in mitochondria, focusing especially on the mechanistic and physiological details of translation termination, and mitoribosome recycling and rescue.

show abstract

Section: The Mitochondrial Translation Cyclementioning

confidence: 87%

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

Section: The Mitochondrial Translation Cyclementioning

confidence: 99%

See 2 more Smart Citations

Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors

Nadler¹,

Lavdovskaia

Richter‐Dennerlein

2021

RNA Biology

View full text Add to dashboard Cite

show abstract

“…Considering the high sequence identity of the enzyme and substrates, it is possible that the mammalian HEMK1 also possesses a methyltransferase activity against human mitochondrial peptide chain release factors (mtRFs). To date, four potential mtRFs have been identi ed in humans, namely MTRF1, MTRF1L, MRPL58 (also known as ICT1), and MTRFR (also known as C12orf65) [20][21][22][23] . As with other class I release factors, all four mtRFs contain the universally conserved GGQ motif.…”

Section: Introductionmentioning

confidence: 99%

Mammalian HEMK1 Methylates Glutamine Residue of the GGQ Motif of Mitochondrial Release Factors

Fang

Kimura

Shimazu

et al. 2021

Preprint

View full text Add to dashboard Cite

Despite limited reports on glutamine methylation, methylated glutamine is found to be highly conserved in a "GGQ" motif in both prokaryotes and eukaryotes. In bacteria, glutamine methylation of peptide chain release factors 1/2 (RF1/2) by the enzyme PrmC is essential for translational termination and transcript recycling. Two PrmC homologs, HEMK1 and HEMK2, are found in mammals. In contrast to those of HEMK2, the biochemical properties and biological significance of HEMK1 remain largely unknown. In this study, we demonstrated that HEMK1 is an active methyltransferase for the glutamine residue of the GGQ motif of all four putative mitochondrial release factors (mtRFs)—MTRF1, MTRF1L, MRPL58, and MTRFR. In HEMK1-deficient HeLa cells, GGQ motif glutamine methylation was absent in all the mtRFs. We examined cell growth and mitochondrial properties, but disruption of the HEMK1 gene had no considerable impact on the overall cell growth, mtDNA copy number, and mitochondrial membrane potential. Furthermore, mitochondrial protein synthesis was not affected in HEMK1 KO cells. Our results suggest that HEMK1 mediates the GGQ methylation of all four mtRFs in human cells; however, this specific modification seems mostly dispensable in cell growth and mitochondrial protein homeostasis under standard culture conditions.

show abstract

Cytochrome c oxidase biogenesis – from translation to early assembly of the core subunit COX1

2023

View full text Add to dashboard Cite

Mitochondria are the powerhouses of the cell as they produce the majority of ATP with their oxidative phosphorylation (OXPHOS) machinery. The OXPHOS system is composed of the F1Fo ATP synthase and four mitochondrial respiratory chain complexes, the terminal enzyme of which is the cytochrome c oxidase (complex IV) that transfers electrons to oxygen, generating water. Complex IV comprises of 14 structural subunits of dual genetic origin: while the three core subunits are mitochondrial encoded, the remaining constituents are encoded by the nuclear genome. Hence, the assembly of complex IV requires the coordination of two spatially separated gene expression machinery. Recent efforts elucidated an increasing number of proteins involved in mitochondrial gene expression, which are linked to complex IV assembly. Additionally, several COX1 biogenesis factors have been intensively biochemically investigated and an increasing number of structural snapshots shed light on the organization of macromolecular complexes such as the mitoribosome or the cytochrome c oxidase. Here, we focus on COX1 translation regulation and highlight the advanced understanding of early steps during COX1 assembly and its link to mitochondrial translation regulation.

show abstract

Structural basis of translation termination, rescue, and recycling in mammalian mitochondria

Cited by 43 publications

References 94 publications

Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors

Maintaining mitochondrial ribosome function: The role of ribosome rescue and recycling factors

Mammalian HEMK1 Methylates Glutamine Residue of the GGQ Motif of Mitochondrial Release Factors

Cytochrome c oxidase biogenesis – from translation to early assembly of the core subunit COX1

Contact Info

Product

Resources

About