bims-mitran 2022-04-17 papers

Issue of 2022–04–17
two papers selected by
Andreas Kohler, Stockholm University

Elife. 2022 Apr 11. pii: e76557. [Epub ahead of print]11

Contingency and selection in mitochondrial genome dynamics.

High frequencies of mutant mitochondrial DNA (mtDNA) in human cells lead to cellular defects that are associated with aging and disease. Yet much remains to be understood about the dynamics of the generation of mutant mtDNAs and their relative replicative fitness that informs their fate within cells and tissues. To address this, we utilize long-read single-molecule sequencing to track mutational trajectories of mtDNA in the model organism Saccharomyces cerevisiae. This model has numerous advantages over mammalian systems due to its much larger mtDNA and ease of artificially competing mutant and wild-type mtDNA copies in cells. We show a previously unseen pattern that constrains subsequent excision events in mtDNA fragmentation in yeast. We also provide evidence for the generation of rare and contentious non-periodic mtDNA structures that lead to persistent diversity within individual cells. Finally, we show that measurements of relative fitness of mtDNA fit a phenomenological model that highlights important biophysical parameters governing mtDNA fitness. Altogether, our study provides techniques and insights into the dynamics of large structural changes in genomes that we show are applicable to more complex organisms like humans.

Keywords: S. cerevisiae; computational biology; genetics; genomics; systems biology

DOI: https://doi.org/10.7554/eLife.76557

Int J Mol Sci. 2022 Mar 23. pii: 3474. [Epub ahead of print]23(7):

Types and Functions of Mitoribosome-Specific Ribosomal Proteins across Eukaryotes.

Vassilis Scaltsoyiannes, Nicolas Corre, Florent Waltz, Philippe Giegé.

Mitochondria are key organelles that combine features inherited from their bacterial endosymbiotic ancestor with traits that arose during eukaryote evolution. These energy producing organelles have retained a genome and fully functional gene expression machineries including specific ribosomes. Recent advances in cryo-electron microscopy have enabled the characterization of a fast-growing number of the low abundant membrane-bound mitochondrial ribosomes. Surprisingly, mitoribosomes were found to be extremely diverse both in terms of structure and composition. Still, all of them drastically increased their number of ribosomal proteins. Interestingly, among the more than 130 novel ribosomal proteins identified to date in mitochondria, most of them are composed of a-helices. Many of them belong to the nuclear encoded super family of helical repeat proteins. Here we review the diversity of functions and the mode of action held by the novel mitoribosome proteins and discuss why these proteins that share similar helical folds were independently recruited by mitoribosomes during evolution in independent eukaryote clades.

Keywords: helical repeat proteins; mitochondrial gene expression; pentatricopeptide repeat proteins; ribosomes; single particle cryo-EM; translation

DOI: https://doi.org/10.3390/ijms23073474