bims-humivi 2025-10-12 papers

Mol Ecol. 2025 Oct 09. e70130

Ancient Introgression Explains Mitochondrial Genome Capture and Mitonuclear Discordance Among South American Collared Tropidurus Lizards.

Matheus M A Salles, André L G Carvalho, Adam D Leaché, Nicolas Martinez, Frederick Bauer, Martha Motte, Viviana Espínola, Miguel T Rodrigues, Carla Piantoni, Marcio R Pie, André Olivotto, Guarino R Colli, Erik L Choueri, Fernanda P Werneck, Fabricius M C B Domingos.

Mitonuclear discordance-evolutionary discrepancies between mitochondrial and nuclear DNA phylogenies-can arise from various factors, including introgression, incomplete lineage sorting, recent or ancient demographic fluctuations, sex-biased dispersal asymmetries, among others. Understanding this phenomenon is crucial for accurately reconstructing evolutionary histories, as failing to account for discordance can lead to misinterpretations of species boundaries, phylogenetic relationships, and historical biogeographic patterns. We investigate the evolutionary drivers of mitonuclear discordance in the Tropidurus spinulosus species group, which contains nine species of lizards inhabiting open tropical and subtropical environments in South America. Using a combination of population genetic and phylogenomic approaches applied to mitochondrial and nuclear data, we identified different instances of gene flow that occurred in ancestral lineages of extant species. Our results point to a complex evolutionary history marked by prolonged isolation between species, demographic fluctuations, and potential episodes of secondary contact with genetic admixture. These conditions likely facilitated mitochondrial genome capture while diluting signals of nuclear introgression. Furthermore, we found no strong evidence supporting incomplete lineage sorting or natural selection as primary drivers of the observed mitonuclear discordance. Therefore, the unveiled patterns are most consistent with neutral demographic processes, coupled with ancient mitochondrial introgression, as the main factors underlying the mismatch between nuclear and mitochondrial phylogenies in this system. Future research could further explore the role of other demographic processes, such as asymmetric sex-biased dispersal, in shaping these complex evolutionary patterns.

Keywords: Phylogenomics; Squamata; introgression; mitogenome; molecular evolution

DOI: https://doi.org/10.1111/mec.70130

Stem Cell Res Ther. 2025 Oct 08. 16(1): 546

Mesenchymal stromal cell-mediated mitochondrial transfer unveils new frontiers in disease therapy.

Huan Chen, Xu Chen, Zi-Hao Zhou, Jia-Rong Zheng, Ye Lu, Pei Lin, Yun-Fan Lin, Yu-Cheng Zheng, Bin Xiong, Rong-Wei Xu, Li Cui, Xin-Yuan Zhao.

Mitochondrial dysfunction is a pivotal factor in the progression of various diseases, making it a critical therapeutic target. Mesenchymal stromal cells (MSCs) have shown promise in mitigating this dysfunction through the transfer of healthy mitochondria to damaged cells. This review comprehensively analyzes the mechanisms of MSC-derived mitochondrial transfer, including tunneling nanotubes (TNTs) and extracellular vesicles, and highlights their therapeutic potential across a spectrum of diseases, such as neurodegenerative disorders, ocular diseases, and inflammatory conditions. Additionally, strategies to enhance mitochondrial transfer efficiency-such as genetic modifications and optimization of MSC sources-are thoroughly explored. Despite these promising findings, challenges remain, including the need for a deeper understanding of transfer mechanisms, ensuring the quality and functionality of transferred mitochondria, and addressing potential immune responses. While MSC-derived mitochondrial transfer holds significant therapeutic potential, careful consideration of its dual nature, especially in specific pathological contexts such as cancer, is essential. With further research and technological advancements, this approach could become a cornerstone in the treatment of diseases characterized by mitochondrial dysfunction.

Keywords: Mesenchymal stromal cell; Mitochondrial transfer; Therapeutic efficacy

DOI: https://doi.org/10.1186/s13287-025-04675-x

Science. 2025 Oct 09. 390(6769): 156-163

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations.

Michele Frison, Brandon S Lockey, Yu Nie, Zoe Golder, Eleni Theiaspra, Cameron D Ryall, Camilla Lyons, Stephen P Burr, Malwina Prater, Lyuba V Bozhilova, Angelos Glynos, James B Stewart, Nick S Jones, Marcos R Chiaratti, Patrick F Chinnery.

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as fast as the nuclear genome, challenging this symbiotic relationship. Mechanisms must have evolved to moderate the impact of mtDNA mutagenesis but are poorly understood. Here, we observed purifying selection of a mouse mtDNA mutation modulated by Ubiquitin-specific peptidase 30 (Usp30) during the maternal-zygotic transition. In vitro, Usp30 inhibition recapitulated these findings by increasing ubiquitin-mediated mitochondrial autophagy (mitophagy). We also found that high mutant burden, or heteroplasmy, impairs the ubiquitin-proteasome system, explaining how mutations can evade quality control to cause disease. Inhibiting USP30 unleashes latent mitophagy, reducing mutant mtDNA in high-heteroplasmy cells. These findings suggest a potential strategy to prevent mitochondrial disorders.

DOI: https://doi.org/10.1126/science.adr5438

Evolution. 2025 Oct 07. pii: qpaf201. [Epub ahead of print]

Reconsidering cytonuclear discordance in the genomic age.

Drew A Larson, Michael W Itgen, Robert D Denton, Matthew W Hahn.

Historically, phylogenetic datasets had relatively few loci but were overrepresented for cytoplasmic sequences (mitochondria and chloroplast) because of their ease of amplification and large numbers of informative sites. Under those circumstances, it made sense to contrast individual gene tree topologies obtained from cytoplasmic loci and nuclear loci, with the goal of detecting differences between them-so-called cytonuclear discordance. In the current age of phylogenomics and ubiquitous gene tree discordance among thousands of loci, it is important to distinguish between simply observing discordance between cytoplasmic trees and a species tree inferred from many nuclear loci and identifying the cause of discordance. Here, we examine what inferences one can make from trees representing different genomic compartments. While topological discordance can be caused by multiple factors, the end goal of many studies is to determine whether the compartments have different evolutionary histories: what we refer to as "cytonuclear dissonance." Answering this question is more complex than simply asking whether there is discordance, requiring additional analyses to determine whether genetic exchange has affected only (or mostly) one compartment. Furthermore, even when these histories differ, expectations about why they differ are not always clear. We conclude by pointing to current research and future opportunities that may help to shed light on topological variation across the multiple genomes contained within a single eukaryotic cell.

DOI: https://doi.org/10.1093/evolut/qpaf201

Biochemistry (Mosc). 2025 Sep;90(9): 1240-1251

Approaches to Humanization of Mitochondrial Proteins in Saccharomyces cerevisiae on the Example of Replacing the Yeast Mitochondrial Translation Termination Factor MRF1 with Its Human Homologues.

Rinat A Khannanov, Ivan V Chicherin, Mariya V Baleva, Sergey A Levitskii, Ruslan A Vasilev, Ulyana E Piunova, Piotr Kamenski.

Mitochondrial translation is a highly specialized process of synthesizing mitochondrially encoded proteins, mainly the components of the oxidative phosphorylation system. It involves four key stages: initiation, elongation, termination, and recycling of mitochondrial ribosomes. Each of these stages is regulated by a specific set of translation factors, most of which are encoded by the nuclear genome and imported into mitochondria. The termination of mitochondrial translation in yeast (Saccharomyces cerevisiae) is carried out by the MRF1 release factor. This nuclear-encoded factor is crucial for ensuring accurate protein synthesis within the organelle, as it recognizes stop codons and facilitates the release of completed polypeptide chains from the ribosome. In addition to this main function, MRF1 participates in maintaining mitochondrial genome stability. The aim of this study was to investigate the capacity of human homologues, hMTRF1, hMTRF1A, and mitoribosome rescue factors hMTRFR and hMRPL58, to compensate for the absence of the yeast mitochondrial translation termination factor MRF1 in S. cerevisiae cells. The results obtained suggest that human orthologues of MRF1, such as hMTRF1 and hMTRF1A, can contribute to maintaining the integrity of the yeast mitochondrial genome. However, they do not fully replace the function of MRF1, as they do not restore normal respiration of the mutant yeast strains.

Keywords: baker’s yeast; humanization; mitochondria; mitochondrial DNA; protein biosynthesis; termination; translation

DOI: https://doi.org/10.1134/S0006297925601418