bims-mitran 2022-09-11 papers

Issue of 2022–09–11
three papers selected by
Andreas Kohler, University of Graz

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

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

Gene. 2022 Sep 02. pii: S0378-1119(22)00595-9. [Epub ahead of print] 146776

Mitochondrial DNA polymorphisms in COX1 affect the lifespan of Caenorhabditis elegans through nuclear gene dct-15.

Yao Zhu, Ying Li, Yuechen Wang, Liang Wang, Peng Shi, Xinze Du, Yingchun Zhang, Yuanjian Song, Zuobin Zhu.

Mutations in the mitochondrial DNA (mtDNA) are closely related to age and age-related complex diseases, but the exact regulatory mechanism of mtDNA natural variation or polymorphism and ageing remains unclear. Recently, nuclear genes that regulate mitochondrial functions and thereby influence ageing have been widely studied. In this study, the relationship between the retrograde communication from the mitochondria to the nucleus and its ultimate effect on ageing has been elucidated. This study found that the natural variations in COX1 of the mitochondria in the Caenorhabditis elegans population do not correlate with multiple phenotypes, except for a mild correlation with lifespan. After excluding the differences in the nuclear genome, the correlation between natural mitochondrial variation and lifespan increased significantly. Moreover, mtDNA variation downregulated the nuclear dct-15 gene expression, which consequently reduced the lifespan, development rate and motility of C. elegans. dct-15 mutations decreased mitochondria copy number but increased ATP content and mitochondrial ultrastructure. Thus, the results indicated that dct-15 interacted with the mitochondrial DNA polymorphisms in COX1 and is associated with ageing. Finally, bioinformatic analyses revealed that mtDNA variation regulated the structural constituent of the cuticle via dct-15 and suggested that the structural constituent of the cuticle could have an important role in the development and ageing processes. These results provide insights into the mtDNA mechanism that can alter the nuclear gene and thereby regulate ageing and ageing-related diseases.

DOI: https://doi.org/10.1016/j.gene.2022.146776