bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–07–06
five papers selected by
Mariangela Santorsola, Università di Pavia



  1. Soc Sci Med. 2025 May 15. pii: S0277-9536(25)00507-6. [Epub ahead of print]382 118177
      'Mitochondrial disease' is an umbrella category for neurogenetic and metabolic diseases which are associated with mitochondrial dysfunction caused by genetic variations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). This article draws on interviews with four mitochondrial disease specialists in Germany in order to explore their perspectives on mitochondrial replacement techniques (MRTs), emerging 'IVF-based technologies' which could potentially prevent the transmission of mitochondrial DNA disease. MRTs aim to exchange (or replace) the cytoplasm of an intended parent's egg cell, which contains disease-causing mtDNA, with the cytoplasm from an egg cell of another individual (aka the mitochondrial donor). MRTs are legal and regulated by assisted reproduction legislation in the UK (since 2015) and Australia (since 2022) for the explicit purpose of reducing the risk of transmitting an mtDNA variant associated with a high risk of severe mitochondrial disease. MRTs are not available in Germany. In other countries, MRTs are offered by fertility clinics for a variety of indications, ranging from the prevention of mitochondrial disease to broader experiences of fertility difficulties. Mitochondrial disease specialists in Germany emphasized the predictability of mitochondrial unpredictability and a mitochondrial disease severity spectrum. Closely engaging with the use of two concepts by the specialists I interviewed-'predictability/unpredictability' and 'severity'-which also appeared in formal and public representations and discussions in the UK, I show how the invocation of these notions may paradoxically both enable and curtail support for the clinical implementation of MRTs.
    Keywords:  Assisted reproduction; Mitochondrial disease; Mitochondrial replacement techniques; Predictability; Rare disease; Severity spectrum; Unpredictability
    DOI:  https://doi.org/10.1016/j.socscimed.2025.118177
  2. Trends Cancer. 2025 Jul 02. pii: S2405-8033(25)00153-0. [Epub ahead of print]
      Sublethal apoptotic stress causing the permeabilization of some mitochondria coupled with cytosolic mitochondrial DNA (mtDNA) accumulation is known to promote cellular senescence. Lai et al. have recently demonstrated that this may be accompanied by mtDNA release within extracellular vesicles that promote local immunosuppression via myeloid-derived suppressor cells.
    Keywords:  NF-κB; PD-L1; SASP; STING; VDAC; prostate cancer
    DOI:  https://doi.org/10.1016/j.trecan.2025.06.010
  3. Sci Rep. 2025 Jul 01. 15(1): 21751
      This study investigated the impact of mitochondrial dynamics on mouse preimplantation embryonic development and its underlying molecular mechanisms. Using pharmacological and genetic approaches, we demonstrated that balanced mitochondrial fusion and fission are essential for optimal embryonic development. Disruption of mitochondrial dynamics significantly impaired blastocyst formation, altered cell lineage allocation, and compromised energy metabolism. Our findings revealed that mitochondrial dynamics regulate gene expression through epigenetic modifications and influence cell survival through the modulation of apoptotic pathways. We also identified key metabolic intermediates and signaling pathways that mediate the effects of mitochondrial dynamics on embryonic development. These results provide new insights into the molecular mechanisms linking mitochondrial function to early embryonic development and suggest potential strategies for improving assisted reproductive technologies.
    Keywords:  Apoptosis; Cell fate; Energy metabolism; Epigenetic modification; Mitochondrial dynamics; Mitochondrial fission; Mitochondrial fusion; Mouse embryo; Preimplantation embryonic development; Reproductive biology
    DOI:  https://doi.org/10.1038/s41598-025-05622-9
  4. Nat Commun. 2025 Jul 01. 16(1): 5709
      Mitochondrial dysfunction contributes to aging and diseases like neurodegeneration and cardiovascular disorders. Mitochondria transfer and transplantation (MTT) represent promising therapeutic strategies aimed at restoring cellular function by introducing functional mitochondria into damaged cells. However, challenges like transfer efficiency, stability, and cellular integration limit clinical application. Recent biotechnological advances-such as liposomes, extracellular vesicles, and surface modifications-enhance mitochondrial protection, targeting, and biocompatibility. This Perspective highlights recent progress in MTT, its therapeutic potential, and current limitations. We also discuss the need for scalable, clinically translatable approaches and appropriate regulatory frameworks to realize the full potential of mitochondria-based nanotherapies in modern medicine.
    DOI:  https://doi.org/10.1038/s41467-025-61239-6
  5. Cell Death Dis. 2025 Jul 01. 16(1): 473
      Mitochondria, often referred to the powerhouse of the cell, are essential for cellular energy production, and their dysfunction can profoundly affect various organs. Transplantation of healthy mitochondria can restore the bioenergetics in diseased cells and address multiple conditions, but more potentials of this approach remain unclear. In this study, I demonstrated that the source of transplanted mitochondria is not limited by species, as exhibit no significant responses to mitochondria derived from different germlines. Moreover, I identified that metabolic compatibility between the recipient and exogenous mitochondria as a crucial factor in mitochondrial transplantation, which confers unique metabolic properties to recipient cells, enabling them to combat different diseases. Additionally, my findings indicated competitive interactions among mitochondria with varying functions, with more bioenergetic-active mitochondria yielded superior therapeutic benefits. Notably, no upper limit for the bioenhancement provided by exogenous mitochondria has been identified. Based on these insights, I proposes a novel therapeutic approach-adaptive bioenhancement through mitochondrial transplantation.
    DOI:  https://doi.org/10.1038/s41419-025-07643-8