Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia-Ischemia.
Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia-Ischemia.
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新生儿缺氧缺血后线粒体碎裂和线粒体自噬的诱导
DOI：
10.3390/cells11071193
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发表时间：
2022-04-01
期刊：
影响因子：
6
通讯作者：
Hagberg H
中科院分区：
文献类型：
--
作者：
Nair S;Leverin AL;Rocha-Ferreira E;Sobotka KS;Thornton C;Mallard C;Hagberg H
缺氧缺血（HI）导致线粒体应激介导的未成熟脑损伤。如果受损的线粒体不能修复，线粒体透化增强，导致细胞死亡。线粒体的非最佳周转是至关重要的，因为它影响短期和长期的结构和功能恢复以及大脑发育。因此，需要通过线粒体自噬来处理缺陷的线粒体，并通过生物合成来替换它们。我们利用mt-Keima报告小鼠，以量化线粒体形态（分裂，融合）和线粒体自噬及其机制的初级神经元后，氧葡萄糖脱氢酶（OGD）和新生儿HI后的脑切片。通过PCR和Western blotting研究了PARK 2依赖和非依赖的线粒体自噬途径的分子机制。使用活细胞显微镜研究线粒体形态和线粒体自噬。在原代神经元中，我们发现了一个初级分裂波后立即OGD与线粒体自噬显着增加，随后在24小时后恢复分裂的第二阶段。HI后，线粒体自噬在HI后立即上调，随后在第7天出现第二波。蛋白质印迹表明，PINK 1/Parkin依赖和非依赖机制，包括NIX和FUNDC 1，在HI后立即上调，而PINK 1/Parkin机制在HI后7天占主导地位。我们推测，在早期阶段过度的线粒体自噬是一种病理反应，这可能有助于二次能量消耗，而二次线粒体自噬可能参与HI后的再生和修复。
Hypoxia–ischemia (HI) leads to immature brain injury mediated by mitochondrial stress. If damaged mitochondria cannot be repaired, mitochondrial permeabilization ensues, leading to cell death. Non-optimal turnover of mitochondria is critical as it affects short and long term structural and functional recovery and brain development. Therefore, disposal of deficient mitochondria via mitophagy and their replacement through biogenesis is needed. We utilized mt-Keima reporter mice to quantify mitochondrial morphology (fission, fusion) and mitophagy and their mechanisms in primary neurons after Oxygen Glucose Deprivation (OGD) and in brain sections after neonatal HI. Molecular mechanisms of PARK2-dependent and -independent pathways of mitophagy were investigated in vivo by PCR and Western blotting. Mitochondrial morphology and mitophagy were investigated using live cell microscopy. In primary neurons, we found a primary fission wave immediately after OGD with a significant increase in mitophagy followed by a secondary phase of fission at 24 h following recovery. Following HI, mitophagy was upregulated immediately after HI followed by a second wave at 7 days. Western blotting suggests that both PINK1/Parkin-dependent and -independent mechanisms, including NIX and FUNDC1, were upregulated immediately after HI, whereas a PINK1/Parkin mechanism predominated 7 days after HI. We hypothesize that excessive mitophagy in the early phase is a pathologic response which may contribute to secondary energy depletion, whereas secondary mitophagy may be involved in post-HI regeneration and repair.
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影响因子：
4.7
作者：
Ivankovic D;Chau KY;Schapira AH;Gegg ME
通讯作者：
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通讯作者：
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影响因子：
2.9
作者：
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通讯作者：
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