Mitochondrial surface coating with artificial lipid membrane improves the transfer efficacy
書誌事項
- 公開日
- 2022-07-25
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/s42003-022-03719-9
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>Extracellular mitochondria are present and act as non-cell-autonomous signals to support energetic homeostasis. While mitochondria allograft is a promising approach in rescuing neurons, glia, and vascular cells in CNS injury and disease, there are profound limitations in cellular uptake of mitochondria together with the efficacy. Here, we modified mitochondria by coating them with cationic DOTAP mixed with DOPE via a modified inverted emulsion method to improve mitochondrial transfer and efficacy. We initially optimized the method using control microbeads and liposomes followed by using mitochondria isolated from intact cerebral cortex of male adult C57BL/6J mice. After the coating process, FACS analysis indicated that approximately 86% of mitochondria were covered by DOTAP/DOPE membrane. Moreover, the artificial membrane-coated mitochondria (AM-mito) shifted the zeta-potential toward positive surface charge, confirming successful coating of isolated mitochondria. Mitochondrial proteins (TOM40, ATP5a, ACADM, HSP60, COX IV) and membrane potentials were well maintained in AM-mito. Importantly, the coating improved mitochondrial internalization and neuroprotection in cultured neurons. Furthermore, intravenous infusion of AM-mito immediately after focal cerebral ischemia-reperfusion amplified cerebroprotection in vivo. Collectively, these findings indicate that mitochondrial surface coating with artificial lipid membrane is feasible and may improve the therapeutic efficacy of mitochondria allograft.</jats:p>
収録刊行物
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- Communications Biology
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Communications Biology 5 (1), 2022-07-25
Springer Science and Business Media LLC
