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VDAC1 promotes cardiomyocyte autophagy in anoxia/reoxygenation injury via the PINK1/Parkin pathway
- Source :
- Cell biology internationalREFERENCES. 45(7)
- Publication Year :
- 2021
-
Abstract
- Ischemia/reperfusion (I/R) is a well-known injury to the myocardium, but the mechanism involved remains elusive. In addition to the well-accepted apoptosis theory, autophagy was recently found to be involved in the process, exerting a dual role as protection in ischemia and detriment in reperfusion. Activation of autophagy is mediated by mitochondrial permeability transition pore (MPTP) opening during reperfusion. In our previous study, we showed that MPTP opening is regulated by VDAC1, a channel protein located in the outer membrane of mitochondria. Thus, up-regulation of VDAC1 expression is a possible trigger to cardiomyocyte autophagy via an unclear pathway. Here, we established an anoxia/reoxygenation (A/R) model in vitro to simulate the I/R process in vivo. At the end of A/R treatment, VDAC1, Beclin 1 and LC3-II/I were up-regulated, and autophagic vacuoles were increased in cardiomyocytes, which showed a connection of VDAC1 and autophagy development. These variation also led to ROS burst, mitochondrial dysfunction and aggravated apoptosis. Knockdown of VDAC1 by RNAi could alleviate the above-mentioned cellular damages. Additionally, the expression of PINK1 and Parkin were enhanced after A/R injury. Furthermore, Parkin was recruited to mitochondria from the cytosol, which suggested that the PINK1/Parkin autophagic pathway was activated during A/R. Nevertheless, the PINK1/Parkin pathway was effectively inhibited when VDAC1 was knocked-down. Taken together, the A/R-induced cardiomyocyte injury was mediated by VDAC1 up-regulation, which led to cell autophagy via the PINK1/Parkin pathway, and finally aggravated apoptosis. This article is protected by copyright. All rights reserved.
- Subjects :
- 0301 basic medicine
Ubiquitin-Protein Ligases
PINK1
Apoptosis
Myocardial Reperfusion Injury
Vacuole
Mitochondrion
Parkin
Cell Line
03 medical and health sciences
0302 clinical medicine
Autophagy
Animals
Myocytes, Cardiac
Membrane Potential, Mitochondrial
Chemistry
Voltage-Dependent Anion Channel 1
Cell Biology
General Medicine
nervous system diseases
Cell biology
Mitochondria
Rats
030104 developmental biology
Mitochondrial permeability transition pore
030220 oncology & carcinogenesis
VDAC1
Protein Kinases
Subjects
Details
- ISSN :
- 10958355
- Volume :
- 45
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Cell biology internationalREFERENCES
- Accession number :
- edsair.doi.dedup.....a39554a0189e52222d601c7ca677530c