| First Author | Nakai R | Year | 2024 |
| Journal | Nat Metab | PubMed ID | 39223312 |
| Mgi Jnum | J:354532 | Mgi Id | MGI:7735047 |
| Doi | 10.1038/s42255-024-01125-5 | Citation | Nakai R, et al. (2024) Mitochondria transfer-based therapies reduce the morbidity and mortality of Leigh syndrome. Nat Metab |
| abstractText | Mitochondria transfer is a recently described phenomenon in which donor cells deliver mitochondria to acceptor cells(1-3). One possible consequence of mitochondria transfer is energetic support of neighbouring cells; for example, exogenous healthy mitochondria can rescue cell-intrinsic defects in mitochondrial metabolism in cultured rho(0) cells or Ndufs4(-)(/-) peritoneal macrophages(4-7). Exposing haematopoietic stem cells to purified mitochondria before autologous haematopoietic stem cell transplantation allowed for treatment of anaemia in patients with large-scale mitochondrial DNA mutations(8,9), and mitochondria transplantation was shown to minimize ischaemic damage to the heart(10-12), brain(13-15) and limbs(16). However, the therapeutic potential of using mitochondria transfer-based therapies to treat inherited mitochondrial diseases is unclear. Here we demonstrate improved morbidity and mortality of the Ndufs4(-)(/-) mouse model of Leigh syndrome (LS) in multiple treatment paradigms associated with mitochondria transfer. Transplantation of bone marrow from wild-type mice, which is associated with release of haematopoietic cell-derived extracellular mitochondria into circulation and transfer of mitochondria to host cells in multiple organs, ameliorates LS in mice. Furthermore, administering isolated mitochondria from wild-type mice extends lifespan, improves neurological function and increases energy expenditure of Ndufs4(-)(/-) mice, whereas mitochondria from Ndufs4(-)(/-) mice did not improve neurological function. Finally, we demonstrate that cross-species administration of human mitochondria to Ndufs4(-)(/-) mice also improves LS. These data suggest that mitochondria transfer-related approaches can be harnessed to treat mitochondrial diseases, such as LS. |
