دورية أكاديمية
Mitochondrial transfer mediates endothelial cell engraftment through mitophagy.
| العنوان: | Mitochondrial transfer mediates endothelial cell engraftment through mitophagy. |
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| المؤلفون: | Lin RZ; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Im GB; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Luo AC; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA., Zhu Y; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Hong X; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.; Department of Surgery, Harvard Medical School, Boston, MA, USA., Neumeyer J; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA., Tang HW; Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Perrimon N; Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA., Melero-Martin JM; Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA. juan.meleromartin@childrens.harvard.edu.; Department of Surgery, Harvard Medical School, Boston, MA, USA. juan.meleromartin@childrens.harvard.edu.; Harvard Stem Cell Institute, Cambridge, MA, USA. juan.meleromartin@childrens.harvard.edu. |
| المصدر: | Nature [Nature] 2024 May; Vol. 629 (8012), pp. 660-668. Date of Electronic Publication: 2024 May 01. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
| مواضيع طبية MeSH: | Endothelial Cells*/cytology , Endothelial Cells*/metabolism , Endothelial Cells*/transplantation , Ischemia*/metabolism , Ischemia*/therapy , Mitochondria*/metabolism , Mitochondria*/transplantation , Mitophagy* , Cell- and Tissue-Based Therapy*/methods, Animals ; Humans ; Male ; Mice ; Autophagosomes/metabolism ; Energy Metabolism ; Human Umbilical Vein Endothelial Cells/metabolism ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/metabolism ; Mice, Nude ; Protein Kinases/deficiency ; Protein Kinases/metabolism ; Ubiquitin-Protein Ligases/deficiency ; Ubiquitin-Protein Ligases/metabolism |
| مستخلص: | Ischaemic diseases such as critical limb ischaemia and myocardial infarction affect millions of people worldwide 1 . Transplanting endothelial cells (ECs) is a promising therapy in vascular medicine, but engrafting ECs typically necessitates co-transplanting perivascular supporting cells such as mesenchymal stromal cells (MSCs), which makes clinical implementation complicated 2,3 . The mechanisms that enable MSCs to facilitate EC engraftment remain elusive. Here we show that, under cellular stress, MSCs transfer mitochondria to ECs through tunnelling nanotubes, and that blocking this transfer impairs EC engraftment. We devised a strategy to artificially transplant mitochondria, transiently enhancing EC bioenergetics and enabling them to form functional vessels in ischaemic tissues without the support of MSCs. Notably, exogenous mitochondria did not integrate into the endogenous EC mitochondrial pool, but triggered mitophagy after internalization. Transplanted mitochondria co-localized with autophagosomes, and ablation of the PINK1-Parkin pathway negated the enhanced engraftment ability of ECs. Our findings reveal a mechanism that underlies the effects of mitochondrial transfer between mesenchymal and endothelial cells, and offer potential for a new approach for vascular cell therapy. (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.) |
| التعليقات: | Comment in: Nat Rev Cardiol. 2024 Jul;21(7):439. doi: 10.1038/s41569-024-01041-x. (PMID: 38773356) |
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| معلومات مُعتمدة: | R01 AR080086 United States AR NIAMS NIH HHS; R01 HL128452 United States HL NHLBI NIH HHS; R01 HL152133 United States HL NHLBI NIH HHS |
| المشرفين على المادة: | EC 2.3.2.27 (parkin protein) EC 2.7.- (Protein Kinases) EC 2.7.11.1 (PTEN-induced putative kinase) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20240501 Date Completed: 20240515 Latest Revision: 20240621 |
| رمز التحديث: | 20240621 |
| DOI: | 10.1038/s41586-024-07340-0 |
| PMID: | 38693258 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1476-4687 |
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| DOI: | 10.1038/s41586-024-07340-0 |