bims-humivi 2025-09-14 papers

on Human mito-nuclear genetic interplay

Issue of 2025–09–14
two papers selected by
Mariangela Santorsola, Università di Pavia

Abundance of Maternal Mitochondrial Genome Is Dispensable up to the Mitochondrial Genome Activation in Post-Implantation Embryos.
Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.

FASEB J. 2025 Sep 15. 39(17): e70986

Abundance of Maternal Mitochondrial Genome Is Dispensable up to the Mitochondrial Genome Activation in Post-Implantation Embryos.

Miki Shavit, Marie Vancová, Jan Jedlicka, Tomáš Bílý, Mushrek Mahrouk, Jan Cendelin, Kateřina Grygarova, Kristýna Popelková, Zdeněk Tůma, Gabriela Pribanova, Jitka Kuncová, Jan Nevoral.

  Mitochondria in the egg are suggested to be crucial for the onset of new life. However, there is ambiguous knowledge about the necessity for fertilization and early embryonic development. Therefore, we created a conditional Tfam knockout (TfamloxP/loxP; Zp3-Cre) to produce Tfamnull oocytes for investigation of the mitochondrial abundance in oocytes and early embryos. This created mtDNA-depleted eggs, although the abundance of mitochondria did not change. Despite decreased mitochondrial membrane potential, Tfamnull oocytes matured and were fertilized, which led to embryo formation. These Tfamnull eggs were developed into mtDNA-deficient blastocysts. Both TFAM and mtDNA appear to be dispensable for the success of embryo implantation. Tfam expression and mtDNA replication rescue the mtDNA-deficient embryo after implantation, enabling passage through a post-implantation bottleneck, and allowing survivor embryos to develop into healthy individuals. Our findings highlight the uncoupled relationship between mtDNA replication and mitochondrial abundance in the growing oocyte and show the importance of the oocyte bulk mtDNA for successful mitochondrial activation in post-implantation embryos.

Keywords:  embryo; fertilization; mitochondrial; mitochondrion; oocyte; transcription factor A

DOI:  https://doi.org/10.1096/fj.202501179R
Front Biosci (Landmark Ed). 2025 Aug 18. 30(8): 37006

Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.

Ha Rim Shin, Gaheon Lee, Kyung Hwa Kim.

  Mitochondria play crucial roles in maintaining health and influencing disease progression by acting as central regulators of cellular homeostasis and energy production. Dysfunctions in mitochondrial activity are increasingly recognized as key contributors to various pathologies, ultimately impacting healthspan and disease outcomes. However, traditional treatments often do not restore damaged mitochondria to a healthy state. Mitochondrial transplantation, a cellular organelle-based therapy in which mitochondria are introduced into a recipient, has emerged as a novel concept in next-generation therapeutics that overcomes the limitations of current cell-based treatments. This review highlights the unique properties of mitochondria as therapeutic agents, including their ability to restore cellular functions and treat a wide range of diseases. In this review, we focus on the unique role of mitochondria in the regulation of stem cell functions, including stem cell fate, self-renewal, and differentiation. Various perspectives have been explored to better understand mitochondrial transplantation therapy, which harnesses the capacity of mitochondria as living drugs in regenerative medicine, as an innovative strategy to bridge the gap between cell therapy and organelle-based treatments and overcome current clinical barriers.

Keywords:  mesenchymal stem cell; mitochondrial dysfunction; mitochondrial transplantation; organelle transplantation; regenerative medicine

DOI:  https://doi.org/10.31083/FBL37006