Structure of the Human Mitochondrial Ribosome Studied In Situ by Cryoelectron Tomography

Englmeier, Robert; Pfeffer, Stefan; Förster, Friedrich

doi:10.1016/j.str.2017.07.011

Cited by 78 publications

(54 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, a group with broad-based mutual interactions, uL3m, bL19m, uL14m, bL17m, uL22m, and bL32m, appears to anchor binding of mL39 and, later, mL45, which also has minimal direct RNA contact. The incorporation of mL45 at an early stage may serve to tether the 39S subunit at the inner membrane during subsequent steps in assembly (Englmeier et al, 2017; Greber et al, 2014). …”

Section: Resultsmentioning

confidence: 99%

Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly

et al. 2018

View full text Add to dashboard Cite

Summary Mammalian mtDNA encodes only 13 proteins, all essential components of respiratory complexes, synthesized by mitochondrial ribosomes. Mitoribosomes contain greatly truncated RNAs transcribed from mtDNA, including a structural tRNA in place of 5S RNA as a scaffold for binding 82 nucleus-encoded proteins, mitoribosomal proteins (MRPs). Cryoelectron microscopy (cryo-EM) studies have determined the structure of the mitoribosome, but its mechanism of assembly is unknown. Our SILAC pulse-labeling experiments determine the rates of mitochondrial import of MRPs and their assembly into intact mitoribosomes, providing a basis for distinguishing MRPs that bind at early and late stages in mitoribosome assembly to generate a working model for mitoribosome assembly. Mitoribosome assembly is a slow process initiated at the mtDNA nucleoid driven by excess synthesis of individual MRPs. MRPs that are tightly associated in the structure frequently join the complex in a coordinated manner. Clinically significant MRP mutations reported to date affect proteins that bind early on during assembly.

show abstract

Section: Resultsmentioning

confidence: 99%

Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Our IFA data suggest that these three proteins are likely mitoribosomal proteins in the Plasmodium mitochondrion ( Figure 2). Since mitoribosomes translate highly hydrophobic proteins of the mtETC, the exit tunnel is generally positioned toward the mitochondrial inner membrane (MIM) and directly contacts the MIM (40). This close interaction of mitoribosomes and MIM facilitates cotranslational insertion of the multitransmembrane protein products into the mtETC, which has been observed in mitochondria of several organisms (40).…”

Section: Pfmtrps18 Appears To Be Located On the Mitochondrial Inner Mmentioning

confidence: 99%

“…Compared to other ribosomes, a unique feature of the mitoribosome is that all or most of its protein translation products are highly hydrophobic mtETC subunits. Studies of mammalian mitoribosomes with cryo-electron tomography have clearly shown the physical attachment of the mitoribosome to the MIM (40). In yeast and mammals, an increasing list of factors has been found that participate in mediating the interaction of the mitoribosome and the MIM in a structure called the mitoribosomal interactome.…”

Section: How Is a Mitoribosome Attached To The Mitochondrial Inner Mementioning

confidence: 99%

Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions

Ling

Maruthi

Munro

et al. 2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

The mitochondrion of malaria parasites contains several clinically validated drug targets. Within Plasmodium spp., the causative agents of malaria, the mitochondrial DNA (mtDNA) is only 6 kb long, being the smallest mitochondrial genome among all eukaryotes. The mtDNA encodes only three proteins of the mitochondrial electron transport chain and ∼27 small, fragmented rRNA genes having lengths of 22–195 nucleotides. The rRNA fragments are thought to form a mitochondrial ribosome (mitoribosome), together with ribosomal proteins imported from the cytosol. The mitoribosome of Plasmodium falciparum is essential for maintenance of the mitochondrial membrane potential and parasite viability. However, the role of the mitoribosome in sustaining the metabolic status of the parasite mitochondrion remains unclear. The small ribosomal subunit in P. falciparum has 14 annotated mitoribosomal proteins, and employing a CRISPR/Cas9-based conditional knockdown tool, here we verified the location and tested the essentiality of three candidates (PfmtRPS12, PfmtRPS17, and PfmtRPS18). Using immuno-EM, we provide evidence that the P. falciparum mitoribosome is closely associated with the mitochondrial inner membrane. Upon knockdown of the mitoribosome, parasites became hypersensitive to inhibitors targeting mitochondrial Complex III (bc1), dihydroorotate dehydrogenase (DHOD), and the F1F0-ATP synthase complex. Furthermore, the mitoribosome knockdown blocked the pyrimidine biosynthesis pathway and reduced the cellular pool of pyrimidine nucleotides. These results suggest that disruption of the P. falciparum mitoribosome compromises the metabolic capacity of the mitochondrion, rendering the parasite hypersensitive to a panel of inhibitors that target mitochondrial functions.

show abstract

“…Cryo-EM reconstruction of the yeast mitoribosome has revealed two distinct membrane contact sites formed, respectively, by the mitochondrial inner membrane protein Mba1 and the expansion segment (96-ES1) in the mtLSU rRNA [37]. The mtrRNA-mediated contact site of the mitoribosome with IMM is absent in mammals while the human homologue of Mba1 (mL45) integrated in the large ribosomal subunit creates a single major contact site with the inner membrane [38].…”

Section: Association Of Mitoribosomes With the Inner Mitochondrial Mementioning

confidence: 99%

An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight

Tomal

Kwasniak-Owczarek

Janska

2019

Cells

View full text Add to dashboard Cite

Contrary to the widely held belief that mitochondrial ribosomes (mitoribosomes) are highly similar to bacterial ones, recent experimental evidence reveals that mitoribosomes do differ significantly from their bacterial counterparts. This review is focused on plant mitoribosomes, but we also highlight the most striking similarities and differences between the plant and non-plant mitoribosomes. An analysis of the composition and structure of mitoribosomes in trypanosomes, yeast, mammals and plants uncovers numerous organism-specific features. For the plant mitoribosome, the most striking feature is the enormous size of the small subunit compared to the large one. Apart from the new structural information, possible functional peculiarities of different types of mitoribosomes are also discussed. Studies suggest that the protein composition of mitoribosomes is dynamic, especially during development, giving rise to a heterogeneous populations of ribosomes fulfilling specific functions. Moreover, convincing data shows that mitoribosomes interact with components involved in diverse mitochondrial gene expression steps, forming large expressosome-like structures.

show abstract

Structure of the Human Mitochondrial Ribosome Studied In Situ by Cryoelectron Tomography

Cited by 78 publications

References 42 publications

Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly

Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly

Genetic ablation of the mitoribosome in the malaria parasite Plasmodium falciparum sensitizes it to antimalarials that target mitochondrial functions

An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight

Contact Info

Product

Resources

About