bims-humivi 2025-07-20 papers

Issue of 2025–07–20
three papers selected by
Mariangela Santorsola, Università di Pavia

bioRxiv. 2025 Jun 23. pii: 2025.01.30.635158. [Epub ahead of print]

Admixture mapping reveals evidence for multiple mitonuclear incompatibilities in swordtail fish hybrids.

Nemo V Robles, Benjamin M Moran, María José Rodríguez-Barrera, Gaston I Jofre, Theresa Gunn, Erik N K Iverson, Sofia Beskid, J J Baczenas, Alisa Sedghifar, Peter Andolfatto, Daniel L Powell, Yaniv Brandvain, Justin C Havird, Gil G Rosenthal, Molly Schumer.

How barriers to gene flow arise between closely related species is one of the oldest questions in evolutionary biology. Classic models in evolutionary biology predict that negative epistatic interactions between variants in the genomes of diverged lineages, known as hybrid incompatibilities, will reduce viability or fertility in hybrids. The genetic architecture of these interactions and the evolutionary paths through which they arise have profound implications for the efficacy of hybrid incompatibilities as barriers to gene flow between species. While these questions have been studied using theoretical approaches for several decades, only recently has it become possible to genetically map larger numbers of hybrid incompatibilities. Here, we use admixture mapping in natural hybrid populations of swordtail fish ( Xiphophorus ) to identify hybrid incompatibilities involving genetic interactions between the mitochondrial and nuclear genomes. We find that at least nine regions of the genome are involved in mitonuclear incompatibilities. These incompatibilities involve interactions between the nuclear genome and the X. malinche mitochondria, the X. birchmanni mitochondria, or both. Moreover, they vary in the strength of selection they experience, and the degree to which they limit gene flow in natural hybrid populations. Our results build a deeper understanding of the complex architecture of selection against incompatibilities in naturally hybridizing species and highlight an important role of mitonuclear interactions in the evolution of reproductive barriers between closely related species.

DOI: https://doi.org/10.1101/2025.01.30.635158

Curr Opin Hematol. 2025 Jul 15.

Megakaryocytes as mitochondria factories: potential donors for mitochondria transplantation.

Émilie Mercure, Martin Pelletier, Éric Boilard.

PURPOSE OF REVIEW: There is an increasing recognition that mitochondria are dynamic regulators of cell fate. Mitochondria transplantation has emerged as a promising therapeutic strategy for conditions ranging from metabolic disorders to neurodegenerative diseases. Thus, there is a growing need for scalable mitochondrial sources for transplantation. We highlight megakaryocytes, best known for their role in platelet production, as a novel and versatile candidate source for mitochondria transplantation.
RECENT FINDINGS: Megakaryocytes are naturally equipped to package and deliver functional mitochondria when producing platelets. Furthermore, MKs can share their mitochondria with neighboring cells in the bone marrow. Given the abundance of mitochondria in megakaryocytes, they may represent an ideal source of mitochondria for transplantation. A better understanding of the role of mitochondria in megakaryocyte heterogeneity and metabolic functions may help harness megakaryocytes for therapeutic transplantation applications.
SUMMARY: Megakaryocyte-derived mitochondria transplantation offers a promising avenue for treating metabolic disorders, leveraging existing mechanisms. Future research should address limitations in megakaryocyte biogenesis and heterogeneity, and optimize delivery systems to maximize therapeutic efficacy.

Keywords: cell therapy; megakaryocytes; mitochondria transplantation

DOI: https://doi.org/10.1097/MOH.0000000000000889

N Engl J Med. 2025 Jul 16.

Mitochondrial Donation and Preimplantation Genetic Testing for mtDNA Disease.

BACKGROUND: Children born to women who carry pathogenic variants in mitochondrial DNA (mtDNA) are at risk for a range of clinical syndromes collectively known as mtDNA disease. Mitochondrial donation by pronuclear transfer involves transplantation of nuclear genome from a fertilized egg from the affected woman to an enucleated fertilized egg donated by an unaffected woman. Thus, pronuclear transfer offers affected women the potential to have a genetically related child with a reduced risk of mtDNA disease.
METHODS: We offered mitochondrial donation (by pronuclear transfer) or preimplantation genetic testing (PGT) to a series of women with pathogenic mtDNA variants who sought to reduce the transmission of these variants to their children. Patients with heteroplasmy (variants present in a proportion of copies of mtDNA) were offered PGT, and patients with homoplasmy (variants present in all copies of mtDNA) or elevated heteroplasmy were offered pronuclear transfer.
RESULTS: Clinical pregnancies were confirmed in 8 of 22 patients (36%) and 16 of 39 patients (41%) who underwent an intracytoplasmic sperm injection procedure for pronuclear transfer or for PGT, respectively. Pronuclear transfer resulted in 8 live births and 1 ongoing pregnancy. PGT resulted in 18 live births. Heteroplasmy levels in the blood of the 8 infants whose mothers underwent pronuclear transfer ranged from undetectable to 16%. Levels of the maternal pathogenic mtDNA variant were 95 to 100% lower in 6 newborns and 77 to 88% lower in 2 newborns than in the corresponding enucleated zygotes. Heteroplasmy levels were known for 10 of the 18 infants whose mothers underwent PGT and ranged from undetectable to 7%.
CONCLUSIONS: We found that mitochondrial donation through pronuclear transfer was compatible with human embryo viability. An integrated program involving pronuclear transfer and PGT was effective in reducing the transmission of homoplasmic and heteroplasmic pathogenic mtDNA variants. (Funded by NHS England and others.).

DOI: https://doi.org/10.1056/NEJMoa2415539