bims-mitran 2025-01-26 papers

Issue of 2025–01–26
three papers selected by
Andreas Kohler, Umeå University

Nat Commun. 2025 Jan 18. 16(1): 817

Numerous rRNA molecules form the apicomplexan mitoribosome via repurposed protein and RNA elements.

Shikha Shikha, Victor Tobiasson, Mariana Ferreira Silva, Jana Ovciarikova, Dario Beraldi, Alexander Mühleip, Lilach Sheiner.

Mitochondrial ribosomes (mitoribosomes) are essential, and their function of synthesising mitochondrial proteins is universal. The core of almost all mitoribosomes is formed from a small number of long and self-folding rRNA molecules. In contrast, the mitoribosome of the apicomplexan parasite Toxoplasma gondii assembles from over 50 extremely short rRNA molecules. Here, we use cryo-EM to discover the features that enable this unusual mitoribosome to perform its function. We reveal that poly-A tails added to rRNA molecules are integrated into the ribosome, and we demonstrate their essentiality for mitoribosome formation and for parasite survival. This is a distinct function for poly-A tails, which are otherwise known primarily as stabilisers of messenger RNAs. Furthermore, while ribosomes typically consist of unique rRNA sequences, here nine sequences are used twice, each copy integrated in a different mitoribosome domain, revealing one of the mechanisms enabling the extreme mitochondrial genome reduction characteristic to Apicomplexa and to a large group of related microbial eukaryotes. Finally, several transcription factor-like proteins are repurposed to compensate for reduced or lost critical ribosomal domains, including members of the ApiAP2 family thus far considered to be DNA-binding transcription factors.

DOI: https://doi.org/10.1038/s41467-025-56057-9

DNA Repair (Amst). 2025 Jan 17. pii: S1568-7864(25)00008-4. [Epub ahead of print]146 103812

Long-range PCR as a tool for evaluating mitochondrial DNA damage: Principles, benefits, and limitations of the technique.

Artem P Gureev, Veronika V Nesterova, Irina S Sadovnikova.

Mitochondrial DNA (mtDNA) is often more susceptible to damage compared to nuclear DNA. This is due to its localization in the mitochondrial matrix, where a large portion of reactive oxygen species are produced. Mitochondria do not have histones and mtDNA is only slightly protected by histone-like proteins and is believed to have less efficient repair mechanisms. In this review, we discuss the long-range PCR method, which allows for the effective detection of mtDNA damage. The method is based on the assumption that various types of DNA lesions can interfere the progress of DNA polymerase, resulting in reduced amplification efficiency. It can be used to estimate the number of additional (above background) lesions in mtDNA. The review outlines the evolution of the methodology, its variations, applications in a wide range of model organisms, the advantages of the method and its limitations, as well as ways to overcome these limitations. Over the past two decades, the use of long-range PCR has allowed the study of mtDNA repair mechanisms, the characteristics of mitochondrial genome damage in various neurodegenerative diseases, aging, ischemic and oncological processes, as well as in anticancer therapy. The assessment of mtDNA damage has also been proposed for use in environmental biomonitoring. This review provides a critical evaluation of the various variations of this method, summarizes the accumulated data, and discusses the role of mtDNA damage in different organs at the organismal level.

Keywords: DNA polymerase; DNA repair; long-range PCR; mitochondrial DNA

DOI: https://doi.org/10.1016/j.dnarep.2025.103812

iScience. 2025 Jan 17. 28(1): 111611

Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila.

Heidi Bretscher, Michael B O'Connor.

Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA). We show that motoneuron to muscle signaling by the TGFβ/Activin family member Actβ positively regulates glycogen levels during Drosophila development. Remarkably, we find that levels of stored glycogen are unaffected by altering cytoplasmic glucose catabolism. Instead, loss of Actβ reduces levels of nuclearly encoded genes required for mtDNA replication, transcription, and translation and mtDNA levels. Direct RNAi knockdown of nuclearly encoded mtDNA expression factors in muscle also results in decreased glycogen stores. Lastly, expressing an activated form of the type I receptor Baboon in muscle restores both glycogen and mtDNA levels in actβ mutants, thereby confirming a direct link between Actβ signaling, glycogen homeostasis, and mtDNA expression factors.

Keywords: Cell biology; Molecular biology

DOI: https://doi.org/10.1016/j.isci.2024.111611