Activated Drp1 Initiates the Formation of Endoplasmic Reticulum‐Mitochondrial Contacts via Shrm4‐Mediated Actin Bundling

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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Activated Drp1 Initiates the Formation of Endoplasmic Reticulum‐Mitochondrial Contacts via Shrm4‐Mediated Actin Bundling ; day:01 ; month:11 ; year:2023 ; extent:14
Advanced science ; (01.11.2023) (gesamt 14)

Creator
Duan, Chenyang
Liu, Ruixue
Kuang, Lei
Zhang, Zisen
Hou, Dongyao
Zheng, Danyang
Xiang, Xinming
Huang, He
Liu, Liangming
Li, Tao

DOI
10.1002/advs.202304885
URN
urn:nbn:de:101:1-2023110114385831029180
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:58 AM CEST

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Associated

  • Duan, Chenyang
  • Liu, Ruixue
  • Kuang, Lei
  • Zhang, Zisen
  • Hou, Dongyao
  • Zheng, Danyang
  • Xiang, Xinming
  • Huang, He
  • Liu, Liangming
  • Li, Tao

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