期刊
CELLS
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cells11071193
关键词
mitochondria; metabolism; mitochondrial fission; neonatal brain injury; reactive oxygen species; neonatal hypoxia-ischemia; mitophagy
类别
资金
- ERA-net (EU) [VR 529-2014-7551]
- Wellcome Trust [WT094823]
- Swedish Medical Research Council (VR) [2019-01320, 2017-01409]
- Swedish Governmental Grant [ALFGBG-432291, ALFGBG-722491]
- Hjarnfonden (Brain Foundation) [FO2019-0056, FO2019-0270]
- ERA-NET [0755101]
- EU [874721]
- Ahlen Foundation
- Tore Nilsons Foundation [2018-00594]
- Jane and Dan Olssson Foundation [2020-25]
- Stiftelsen Fru Mary Von Sydows [3616]
- Hasselblad Foundation
- Ake Wibergs Foundation [M19-0660]
- Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre
- King's College London
- King's College Hospital NHS Foundation Trust
- Swedish Research Council [2019-01320, 2017-01409] Funding Source: Swedish Research Council
Hypoxia-ischemia (HI) leads to immature brain injury mediated by mitochondrial stress. The turnover of mitochondria, including mitophagy and biogenesis, is critical for brain development and functional recovery. Excessive mitophagy in the early phase may be pathological, leading to secondary energy depletion, while secondary mitophagy may contribute to post-HI regeneration and repair.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据