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Tripartite Motif Containing 65 Deficiency Confers Protection Against Acute Kidney Injury via Alleviating
Tao Chen1,2,3, Yang Zhang1, Liting Ding2
1Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College Nanchang University Nanchang China.
Medcomm
|April 23, 2025
Summary
Tripartite motif containing 65 (TRIM65) is upregulated in acute kidney injury (AKI). TRIM65 deficiency protects against AKI by stabilizing voltage-dependent anion channel 1 (VDAC1), preventing mitochondrial dysfunction.
Area of Science:
- Nephrology
- Molecular Biology
- Cellular Biology
Background:
- Acute kidney injury (AKI) is a common clinical condition with high morbidity and mortality.
- Current therapeutic strategies for AKI are limited due to incomplete understanding of its complex pathology.
- Tripartite motif containing 65 (TRIM65) is known to regulate inflammation, but its role in AKI is unexplored.
Purpose of the Study:
- To investigate the role of TRIM65 in the pathogenesis of AKI.
- To elucidate the molecular mechanisms by which TRIM65 influences AKI.
- To explore TRIM65 as a potential therapeutic target for AKI.
Main Methods:
- Assessed TRIM65 expression in AKI models.
- Utilized TRIM65 knockout mice to evaluate its protective effects against various AKI types (rhabdomyolysis, ischemia-reperfusion, cisplatin-induced).
- Investigated the interaction between TRIM65 and voltage-dependent anion channel 1 (VDAC1), including ubiquitination sites and effects on VDAC1 stability and autophagy.
- Examined the impact of TRIM65 deficiency on mitochondrial function in renal tubular epithelial cells.
- Assessed the effect of VDAC1 overexpression on TRIM65 deficiency-mediated protection in AKI.
Main Results:
- TRIM65 expression was found to be upregulated in AKI.
- TRIM65 knockout mice showed significant protection against multiple forms of AKI.
- TRIM65 was identified to directly bind and mediate polyubiquitination of VDAC1 at K161 and K200, enhancing VDAC1 stability and inhibiting its autophagic degradation.
- TRIM65 deficiency ameliorated mitochondrial dysfunction in renal tubular cells during AKI.
- Overexpression of VDAC1 reversed the protective effects of TRIM65 deficiency in AKI.
Conclusions:
- TRIM65 plays a critical role in AKI development by regulating VDAC1 stability and VDAC1-dependent mitochondrial function.
- Targeting the TRIM65-VDAC1 axis presents a potential therapeutic strategy for AKI.
- Further research into TRIM65 and VDAC1 could lead to novel treatments for acute kidney injury.
Keywords:
acute kidney injury (AKI)mitochondrial dysfunctiontripartite motif containing 65 (TRIM65)ubiquitinationvoltage‐dependent anion channel 1 (VDAC1)More Related Videos
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