bims-tricox 2022-09-11 papers

bims-tricox

Biomed News

on Translation, ribosomes and COX

Issue of 2022‒09‒11
seven papers selected by
Yash Verma
University of Delhi South Campus

Mechanisms and players of mitoribosomal biogenesis revealed in trypanosomatids.
The dark side of the ribosome life cycle.
Mitochondrial protein synthesis and the bioenergetic cost of neurodevelopment.
Something old, something new, something borrowed, something blue: the anaerobic microbial ancestry of aerobic respiration.
Mitochondrial respiratory complexes: Significance in human mitochondrial disorders and cancers.
Maintenance of tRNA and elongation factors supports T3SS proteins translational elongations in pathogenic bacteria during nutrient starvation.
Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.

Trends Parasitol. 2022 Sep 05. pii: S1471-4922(22)00187-8. [Epub ahead of print]

Mechanisms and players of mitoribosomal biogenesis revealed in trypanosomatids.

Ondřej Gahura, Prashant Chauhan, Alena Zíková.

  Translation in mitochondria is mediated by mitochondrial ribosomes, or mitoribosomes, complex ribonucleoprotein machines with dual genetic origin. Mitoribosomes in trypanosomatid parasites diverged markedly from their bacterial ancestors and other eukaryotic lineages in terms of protein composition, rRNA content, and overall architecture, yet their core functional elements remained conserved. Recent cryo-electron microscopy studies provided atomic models of trypanosomatid large and small mitoribosomal subunits and their precursors, making these parasites the organisms with the best-understood biogenesis of mitoribosomes. The structures revealed molecular mechanisms and players involved in the assembly of mitoribosomes not only in the parasites, but also in eukaryotes in general.

Keywords:  Trypanosoma; assembly factor; biogenesis; mitochondrial ribosomes; mitoribosomes

DOI:  https://doi.org/10.1016/j.pt.2022.08.010
RNA Biol. 2022 Jan;19(1): 1045-1049

The dark side of the ribosome life cycle.

Sébastien Ferreira-Cerca.

  Thanks to genetics, biochemistry, and structural biology many features of the ribosome´s life cycles in models of bacteria, eukaryotes, and some organelles have been revealed to near-atomic details. Collectively, these studies have provided a very detailed understanding of what are now well-established prototypes for ribosome biogenesis and function as viewed from a 'classical' model organisms perspective. However, very important challenges remain ahead to explore the functional and structural diversity of both ribosome biogenesis and function across the biological diversity on earth. Particularly, the 'third domain of life', the archaea, and also many non-model bacterial and eukaryotic organisms have been comparatively neglected. Importantly, characterizing these additional biological systems will not only offer a yet untapped window to enlighten the evolution of ribosome biogenesis and function but will also help to unravel fundamental principles of molecular adaptation of these central cellular processes.

Keywords:  RNA; Ribosome; archaea; non-model organism; ribosome biogenesis

DOI:  https://doi.org/10.1080/15476286.2022.2121421
iScience. 2022 Sep 16. 25(9): 104920

Mitochondrial protein synthesis and the bioenergetic cost of neurodevelopment.

Pernille Bülow, Anupam Patgiri, Victor Faundez.

  The human brain consumes five orders of magnitude more energy than the sun by unit of mass and time. This staggering bioenergetic cost serves mostly synaptic transmission and actin cytoskeleton dynamics. The peak of both brain bioenergetic demands and the age of onset for neurodevelopmental disorders is approximately 5 years of age. This correlation suggests that defects in the machinery that provides cellular energy would be causative and/or consequence of neurodevelopmental disorders. We explore this hypothesis from the perspective of the machinery required for the synthesis of the electron transport chain, an ATP-producing and NADH-consuming enzymatic cascade. The electron transport chain is constituted by nuclear- and mitochondrial-genome-encoded subunits. These subunits are synthesized by the 80S and the 55S ribosomes, which are segregated to the cytoplasm and the mitochondrial matrix, correspondingly. Mitochondrial protein synthesis by the 55S ribosome is the rate-limiting step in the synthesis of electron transport chain components, suggesting that mitochondrial protein synthesis is a bottleneck for tissues with high bionergetic demands. We discuss genetic defects in the human nuclear and mitochondrial genomes that affect these protein synthesis machineries and cause a phenotypic spectrum spanning autism spectrum disorders to neurodegeneration during neurodevelopment. We propose that dysregulated mitochondrial protein synthesis is a chief, yet understudied, causative mechanism of neurodevelopmental and behavioral disorders.

Keywords:  Biological Sciences; Cell Biology; Neuroscience

DOI:  https://doi.org/10.1016/j.isci.2022.104920
Trends Microbiol. 2022 Sep 01. pii: S0966-842X(22)00218-9. [Epub ahead of print]

Something old, something new, something borrowed, something blue: the anaerobic microbial ancestry of aerobic respiration.

Jennifer B Glass, Claire E Elbon, Loren Dean Williams.

  Aerobic respiration evolved by bricolage, with modules cobbled together as microbial biochemistry coevolved with Earth's geochemistry. The mitochondrial electron transport chain represents a patchwork of respiratory modules inherited from microbial methanogenesis, iron oxidation, anoxygenic photosynthesis, and denitrification pathways, and preserves a biochemical record of Earth's redox environment over its four-billion-year history. Imprints of the anoxic early Earth are recognizable in Complex I's numerous iron-sulfur cofactors and vestigial binding sites for ferredoxin, nickel-iron, and molybdopterin, whereas the more recent advent of oxygen as a terminal electron acceptor necessitated use of heme and copper cofactors by Complex IV. Bricolage of respiratory complexes resulted in supercomplexes for improved electron transfer efficiency in some bacteria and archaea, and in many eukaryotes. Accessory subunits evolved to wrap mitochondrial supercomplexes for improved assembly and stability. Environmental microbes with 'fossil' proteins that are similar to ancestral forms of the respiratory complexes deserve further scrutiny and may reveal new insights on the evolution of aerobic respiration.

Keywords:  aerobic; anaerobic; electron transport chain; evolution; respiration

DOI:  https://doi.org/10.1016/j.tim.2022.08.006
J Cell Physiol. 2022 Sep 08.

Mitochondrial respiratory complexes: Significance in human mitochondrial disorders and cancers.

Kunwar Somesh Vikramdeo, Sarabjeet Kour Sudan, Ajay P Singh, Seema Singh, Santanu Dasgupta.

  Mitochondria are pivotal organelles that govern cellular energy production through the oxidative phosphorylation system utilizing five respiratory complexes. In addition, mitochondria also contribute to various critical signaling pathways including apoptosis, damage-associated molecular patterns, calcium homeostasis, lipid, and amino acid biosynthesis. Among these diverse functions, the energy generation program oversee by mitochondria represents an immaculate orchestration and functional coordination between the mitochondria and nuclear encoded molecules. Perturbation in this program through respiratory complexes' alteration results in the manifestation of various mitochondrial disorders and malignancy, which is alarmingly becoming evident in the recent literature. Considering the clinical relevance and importance of this emerging medical problem, this review sheds light on the timing and nature of molecular alterations in various respiratory complexes and their functional consequences observed in various mitochondrial disorders and human cancers. Finally, we discussed how this wealth of information could be exploited and tailored to develop respiratory complex targeted personalized therapeutics and biomarkers for better management of various incurable human mitochondrial disorders and cancers.

Keywords:  ATP; cancer; genetic disorders; mitochondria; oxidative phosphorylation (OXPHOS); respiratory complexes

DOI:  https://doi.org/10.1002/jcp.30869
Cell Biosci. 2022 Sep 05. 12(1): 147

Maintenance of tRNA and elongation factors supports T3SS proteins translational elongations in pathogenic bacteria during nutrient starvation.

Yue Sun, Xiaolong Shao, Yingchao Zhang, Liangliang Han, Jiadai Huang, Yingpeng Xie, Jingui Liu, Xin Deng.

  BACKGROUND: Sufficient nutrition contributes to rapid translational elongation and protein synthesis in eukaryotic cells and prokaryotic bacteria. Fast synthesis and accumulation of type III secretion system (T3SS) proteins conduce to the invasion of pathogenic bacteria into the host cells. However, the translational elongation patterns of T3SS proteins in pathogenic bacteria under T3SS-inducing conditions remain unclear. Here, we report a mechanism of translational elongation of T3SS regulators, effectors and structural protein in four model pathogenic bacteria (Pseudomonas syringae, Pseudomonas aeruginosa, Xanthomonas oryzae and Ralstonia solanacearum) and a clinical isolate (Pseudomonas aeruginosa UCBPP-PA14) under nutrient-limiting conditions. We proposed a luminescence reporter system to quantitatively determine the translational elongation rates (ERs) of T3SS regulators, effectors and structural protein under different nutrient-limiting conditions and culture durations.RESULTS: The translational ERs of T3SS regulators, effectors and structural protein in these pathogenic bacteria were negatively regulated by the nutrient concentration and culture duration. The translational ERs in 0.5× T3SS-inducing medium were the highest of all tested media. In 1× T3SS-inducing medium, the translational ERs were highest at 0 min and then rapidly decreased. The translational ERs of T3SS regulators, effectors and structural protein were inhibited by tRNA degradation and by reduced levels of elongation factors (EFs).
CONCLUSIONS: Rapid translational ER and synthesis of T3SS protein need adequate tRNAs and EFs in nutrient-limiting conditions. Numeric presentation of T3SS translation visually indicates the invasion of bacteria and provides new insights into T3SS expression that can be applied to other pathogenic bacteria.

Keywords:  Elongation factor; Nutrient-limiting conditions; Pathogenic bacteria; T3SS; Translational elongation rate; tRNA

DOI:  https://doi.org/10.1186/s13578-022-00884-6
Int J Mol Sci. 2022 Aug 26. pii: 9703. [Epub ahead of print]23(17):

Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.

Ying Song, Xin-Yi Zhu, Xiao-Min Zhang, He Xiong.

  Mitochondrial epigenetic alterations are closely related to Alzheimer's disease (AD), which is described in this review. Reports of the alteration of mitochondrial DNA (mtDNA) methylation in AD demonstrate that the disruption of the dynamic balance of mtDNA methylation and demethylation leads to damage to the mitochondrial electron transport chain and the obstruction of mitochondrial biogenesis, which is the most studied mitochondrial epigenetic change. Mitochondrial noncoding RNA modifications and the post-translational modification of mitochondrial nucleoproteins have been observed in neurodegenerative diseases and related diseases that increase the risk of AD. Although there are still relatively few mitochondrial noncoding RNA modifications and mitochondrial nuclear protein post-translational modifications reported in AD, we have reason to believe that these mitochondrial epigenetic modifications also play an important role in the AD process. This review provides a new research direction for the AD mechanism, starting from mitochondrial epigenetics. Further, this review summarizes therapeutic approaches to targeted mitochondrial epigenetics, which is the first systematic summary of therapeutic approaches in the field, including folic acid supplementation, mitochondrial-targeting antioxidants, and targeted ubiquitin-specific proteases, providing a reference for therapeutic targets for AD.

Keywords:  Alzheimer’s disease; methylation; mitochondrial DNA; mitochondrial epigenetics; noncoding RNA; post-translational modification

DOI:  https://doi.org/10.3390/ijms23179703