bims-humivi 2025-05-18 papers

Issue of 2025–05–18
three papers selected by
Mariangela Santorsola, Università di Pavia

Front Immunol. 2025 ;16 1542369

Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation.

Mitochondria, as the primary energy factories of cells, play a pivotal role in maintaining nervous system function and regulating inflammatory responses. The balance of mitochondrial quality control is critical for neuronal health, and disruptions in this balance are often implicated in the pathogenesis of various neurological disorders. Mitochondrial dysfunction not only exacerbates energy deficits but also triggers neuroinflammation through the release of damage-associated molecular patterns (DAMPs), such as mitochondrial DNA (mtDNA) and reactive oxygen species (ROS). This review examines the mechanisms and recent advancements in mitochondrial quality control in neurological diseases, focusing on processes such as mitochondrial fusion and fission, mitophagy, biogenesis, and protein expression regulation. It further explores the role of mitochondrial dysfunction and subsequent inflammatory cascades in conditions such as ischemic and hemorrhagic stroke, neurodegenerative diseases and brain tumors. Additionally, emerging research highlights the significance of mitochondrial transfer mechanisms, particularly intercellular transfer between neurons and glial cells, as a potential strategy for mitigating inflammation and promoting cellular repair. This review provides insights into the molecular underpinnings of neuroinflammatory pathologies while underscoring the translational potential of targeting mitochondrial quality control for therapeutic development.

Keywords: mitochondrial; mitochondrial quality control; mitochondrial transfer; neuroinflammation; neurological disorders

DOI: https://doi.org/10.3389/fimmu.2025.1542369

Eur J Clin Invest. 2025 May 15. e70073

Mesenchymal stem cell-mediated mitochondrial transfer regulates the fate of B lymphocytes.

Veronika Somova, Natalie Jaborova, Bianka Porubska, Daniel Vasek, Natalie Fikarova, Martin Prevorovsky, Zuzana Nahacka, Jiri Neuzil, Magdalena Krulova.

BACKGROUND: Mitochondrial transfer is becoming recognized as an important immunomodulatory mechanism used by mesenchymal stem cells (MSCs) to influence immune cells. While effects on T cells and macrophages have been documented, the influence on B cells remains unexplored. This study investigates the modulation of B lymphocyte fate by MSC-mediated mitochondrial transfer.
METHODS: MSCs labelled with MitoTracker dyes or derived from mito::mKate2 transgenic mice were co-cultured with splenocytes. Flow cytometry assessed mitochondrial transfer, reactive oxygen species (ROS) levels, apoptosis and mitophagy. Glucose uptake was measured using the 2-NBDG assay. RNA sequencing analysed gene expression changes in CD19+ mitochondria recipients and nonrecipients. Pathway analysis identified affected processes. In an LPS-induced inflammation model, mito::mKate2 MSCs were administered, and B cells from different organs were analysed for mitochondrial uptake and phenotypic changes. MSC-derived mitochondria were also isolated to confirm uptake by FACS-sorted CD19+ cells.
RESULTS: MSCs transferred mitochondria to CD19+ cells, though less than to other immune cells. Transfer correlated with ROS levels and mitophagy induction. Mitochondria were preferentially acquired by activated B cells, as indicated by increased CD69 expression and glycolytic activity. Bidirectional transfer occurred, with immune cells exchanging dysfunctional mitochondria for functional ones. CD19+ recipients exhibited increased viability, proliferation and altered gene expression, with upregulated cell division genes and downregulated antigen presentation genes. In vivo, mitochondrial acquisition reduced B cell activation and inflammatory cytokine production. Pre-sorted B cells also acquired isolated mitochondria, exhibiting a similar anti-inflammatory phenotype.
CONCLUSIONS: These findings highlight mitochondrial trafficking as a key MSC-immune cell interaction mechanism with immunomodulatory therapeutic potential.

Keywords: B cell; immunoregulation; mesenchymal stem cell; metabolism; mitochondria

DOI: https://doi.org/10.1111/eci.70073

Int J Mol Sci. 2025 Apr 25. pii: 4098. [Epub ahead of print]26(9):

The Importance of Mitochondrial Processes in the Maturation and Acquisition of Competences of Oocytes and Embryo Culture.

Elżbieta Gałęska, Alicja Kowalczyk, Marcjanna Wrzecińska, Mercedes Camiña García, Ewa Czerniawska-Piątkowska, Szymon Gwoździewicz, Wojciech Witkiewicz, Zbigniew Dobrzański.

Mitochondria, as multifunctional and partially independent structures, play a crucial role in determining essential life processes. Recently, their significance in reproductive biology has gained increasing attention. This review aims to comprehensively analyse the role of mitochondrial processes in oocyte maturation and embryo culture. A comprehensive literature review was conducted to highlight the importance of mitochondrial activity in the early stages of life formation. Proper mitochondrial function provides energy, maintains genomic stability, and ensures optimal conditions for fertilisation and embryo progression. Understanding these processes is essential to optimise culture conditions and identify new mitochondrial biomarkers that improve reproductive success and improve assisted reproductive technologies (ARTs). Enhancing mitochondrial function in female reproductive cells is the key to improving oocyte and embryo quality, which can lead to better in vitro fertilisation and embryo transfer. Furthermore, advances in diagnostic techniques, such as mitochondrial genome sequencing, offer a more precise understanding of the relationship between mitochondrial health and oocyte quality. However, fully understanding mitochondrial functions is only part of the challenge. Expanding knowledge of the interactions between mitochondria and other cellular structures is crucial for future advancements in reproductive medicine. Understanding these complex relationships will provide deeper insight into improving reproductive outcomes and embryo development.

Keywords: embryo culture; maturation; mitochondria; oocytes; reproduction

DOI: https://doi.org/10.3390/ijms26094098