Autor: |
Chenyang Duan, Ruixue Liu, Lei Kuang, Zisen Zhang, Dongyao Hou, Danyang Zheng, Xinming Xiang, He Huang, Liangming Liu, Tao Li |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
Advanced Science, Vol 10, Iss 36, Pp n/a-n/a (2023) |
Druh dokumentu: |
article |
ISSN: |
2198-3844 |
DOI: |
10.1002/advs.202304885 |
Popis: |
Abstract Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER‐Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin‐related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER‐Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER‐Mito contact establishment. Both Drp1 activation and ER‐Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic‐hypoxic conditions. The activated form of Drp1 aids in ER‐Mito contact initiation by recruiting Shrm4 and promoting actin bundling between the ER and mitochondria. This process relies on the structural interplay between INF2 and scattered F‐actin on the ER. This study uncovers new roles of cytoplasmic Drp1, providing valuable insights for devising strategies to manage mitochondrial imbalances in the context of ischemic‐hypoxic injury. |
Databáze: |
Directory of Open Access Journals |
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