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Updated: Mar 3, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
USP30 alleviates intestinal ischemia-reperfusion injury by deubiquitinating MFN2 mediating the mitochondrial
Ziyi Weng1, Tulanisa Kadier1, Ruili Ding1
1Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Abstract:
Intestinal ischemia-reperfusion (IIR) injury can cause intestinal barrier damage, systemic inflammatory response, and high mortality. The key mechanism is the disorder of the mitochondrial-endoplasmic reticulum network. Ubiquitin-specific peptidase 30 (USP30), located on the outer mitochondrial membrane, can reverse the partial ubiquitination of Parkin substrates or completely remove the ubiquitin chain to maintain mitochondrial function. Mitofusin 2 (MFN2) is a mitochondrial outer membrane fusion protein that mediates mitophagy and endoplasmic reticulum stress and participates in the formation of mitochondria-associated endoplasmic reticulum (MAMs). Our research showed that IIR reduces the protein expression of USP30 and MFN2, and overexpression of USP30 can increase the stability of MFN2 through deubiquitination and alleviate the damage caused by IIR. After overexpression of MFN2, mitochondrial dysfunction and endoplasmic reticulum stress caused by IIR are restored, while knockdown of MFN2 weakens the protective effect of USP30 on the MAMs. USP30 alleviates endoplasmic reticulum stress and mitochondrial dysfunction caused by intestinal ischemia-reperfusion injury by reducing the ubiquitination level of MFN2. The regulation of USP30 may be a promising strategy for alleviating intestinal ischemia-reperfusion injury.
Insights
Ubiquitin-specific peptidase 30 (USP30) protects against intestinal ischemia-reperfusion (IIR) injury by stabilizing Mitofusin 2 (MFN2). This action mitigates mitochondrial and endoplasmic reticulum damage, offering a potential therapeutic strategy for IIR.
Area of Science:
- Cell Biology
- Gastroenterology
- Pathophysiology
Background:
- Intestinal ischemia-reperfusion (IIR) injury leads to significant intestinal barrier damage, systemic inflammation, and mortality.
- Mitochondrial-endoplasmic reticulum network disorder is a key mechanism in IIR.
- Ubiquitin-specific peptidase 30 (USP30) and Mitofusin 2 (MFN2) are crucial for mitochondrial function and endoplasmic reticulum stress regulation.
Purpose of the Study:
- To investigate the role of USP30 and MFN2 in IIR.
- To elucidate the mechanism by which USP30 influences MFN2 stability and alleviates IIR.
- To explore USP30 as a potential therapeutic target for IIR.
Main Methods:
- Investigated protein expression levels of USP30 and MFN2 in IIR models.
- Utilized overexpression of USP30 and MFN2, and knockdown of MFN2.
- Assessed mitochondrial function and endoplasmic reticulum stress markers.
Main Results:
- IIR was found to reduce the expression of USP30 and MFN2.
- Overexpression of USP30 increased MFN2 stability via deubiquitination, alleviating IIR-induced damage.
- Overexpression of MFN2 restored mitochondrial function and reduced endoplasmic reticulum stress in IIR, while MFN2 knockdown diminished USP30's protective effects.
Conclusions:
- USP30 alleviates IIR-induced endoplasmic reticulum stress and mitochondrial dysfunction by reducing MFN2 ubiquitination.
- USP30 enhances MFN2 stability, protecting the mitochondria-associated endoplasmic reticulum (MAMs).
- USP30 regulation presents a promising therapeutic strategy for mitigating intestinal ischemia-reperfusion injury.
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