bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–06–15
three papers selected by
Mariangela Santorsola, Università di Pavia



  1. Genome Biol Evol. 2025 Jun 13. pii: evaf123. [Epub ahead of print]
      Mitochondria play a central role in cellular respiration, but require close coevolution with the nuclear genome for proper function. This process, termed mitonuclear coevolution, is poorly understood on species-level evolutionary timescales, despite its role in speciation. Here, we investigate mitonuclear coevolution in bumblebees (Bombus), a group of ecologically diverse pollinators with rapid mitochondrial (mt) DNA evolution. Leveraging genomic data from a comprehensive set of 55 bumblebee species, we quantified the evolutionary rate correlation (ERC) between mt genes and nuclear genes that interact with mitochondria (N-mt). We found a strong ERC between mt and N-mt genes, but not among mt genes and random nuclear genes, supporting the mitonuclear coevolution hypothesis. Additionally, we found the strength of mitonuclear ERC seems to be consistent across bumblebee lineages, contrasting with observations in other taxa. Finally, bumblebee species from colder environments showed increased mt evolutionary rates relative to both N-mt genes and random nuclear genes. This suggests potential implications to bumblebee climatic niche adaptation and the thermoregulation of cold-adapted species, possibly driven by selection for enhanced mt function to sustain thermogenesis and flight in low-temperature environments. Our findings are discussed considering the dynamics of mitonuclear coevolution in bumblebees and its potential role in shaping their adaptation to diverse ecological niches.
    Keywords:  Hymenoptera; local adaptation; mitochondrial DNA; mitonuclear interactions; nuclear compensation; thermogenesis
    DOI:  https://doi.org/10.1093/gbe/evaf123
  2. MedComm (2020). 2025 Jun;6(6): e70253
      Advances in mitochondrial biology have led to the development of mitochondrial transplantation as a novel and promising therapeutic strategy. This review provides a comprehensive analysis of the multifaceted roles of mitochondria in health and disease, highlighting their central functions in energy production, antioxidant defense, calcium signaling, apoptosis regulation, and mitochondrial homeostasis maintenance. We explore the mechanisms by which transplanted mitochondria exert their therapeutic effects, including restoring ATP production, attenuating oxidative stress, modulating inflammatory responses, reducing cellular apoptosis, promoting cell repair and regeneration, facilitating neural circuit reconstruction, and exhibiting antitumor properties. Key preclinical studies demonstrating the efficacy of mitochondrial transplantation across in vitro and in vivo disease models are discussed, along with the status of clinical trials. The review also critically compares mitochondrial transplantation with other mitochondria-targeted therapies, evaluating their relative advantages and limitations. Finally, we discuss the current challenges of translating this innovative therapy into clinical practice, such as mitochondrial isolation and purification, storage, targeted delivery, potential immune responses, and long-term safety and efficacy concerns. This review aims to stimulate further research and development in this promising field, paving the way for novel therapeutic interventions for various diseases.
    Keywords:  disease therapy; mitochondria; mitochondrial transplantation; therapeutic strategy
    DOI:  https://doi.org/10.1002/mco2.70253
  3. JCI Insight. 2025 Jun 10. pii: e187792. [Epub ahead of print]
      Mitochondrial DNA (mtDNA) shares characteristics with bacterial DNA and activates immune cells via Toll like receptor (TLR)-9. Extracellular vesicles (EVs) and mtDNA have been found in blood products and can activate immune cells; we sought to characterize their evolution in stored blood products. From a previous study of hemolysis in 13,403 blood donors, a second blood unit was drawn from 651 donors and sampled at days 10, 21, and 42. EV counts and RBC-EVs increased with storage time, and EV levels were higher in males and in RBC units processed in AS-1 compared to AS-3. mtDNA levels were higher in females and RBC units processed in AS-3. EV populations and mtDNA levels were highly correlated within donors for 98 donations obtained 2-12 months apart. Quantitative trait locus analysis revealed several genetic associations, most notably linking mtDNA levels with polymorphisms in ANKLE1, which encodes an erythroid-specific protein that preferentially cleaves mtDNA. These data suggest that donor-intrinsic factors may influence mtDNA and EV levels found in RBC units. This finding lends impetus to determining if genetic or environmental factors control levels of these immune mediators in blood donors.
    Keywords:  Cell biology; Hematology; Innate immunity
    DOI:  https://doi.org/10.1172/jci.insight.187792