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Journal article
Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction
Journal of Biological Chemistry, Vol.288, pp.915-926
288
2013
PMCID: PMC3543040
PMID: 23152496
Web of Science ID: WOS:000313570300016
Abstract
It is known that loss-of-function mutations in the gene encoding Parkin lead to development of Parkinson disease. Recently, Parkin was found to play an important role in the removal of dysfunctional mitochondria via autophagy in neurons. Although Parkin is expressed in the heart, its functional role in this tissue is largely unexplored. In this study, we have investigated the role of Parkin in the myocardium under normal physiological conditions and in response to myocardial infarction. We found that Parkin-deficient (Parkin(-/-)) mice had normal cardiac function for up to 12 months of age as determined by echocardiographic analysis. Although ultrastructural analysis revealed that Parkin-deficient hearts had disorganized mitochondrial networks and significantly smaller mitochondria, mitochondrial function was unaffected. However, Parkin(-/-) mice were much more sensitive to myocardial infarction when compared with wild type mice. Parkin(-/-) mice had reduced survival and developed larger infarcts when compared with wild type mice after the infarction. Interestingly, Parkin protein levels and mitochondrial autophagy (mitophagy) were rapidly increased in the border zone of the infarct in wild type mice. In contrast, Parkin(-/-) myocytes had reduced mitophagy and accumulated swollen, dysfunctional mitochondria after the infarction. Overexpression of Parkin in isolated cardiac myocytes also protected against hypoxia-mediated cell death, whereas nonfunctional Parkinson disease-associated mutants ParkinR42P and ParkinG430D had no effect. Our results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria.
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- Title
- Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction
- Publication Details
- Journal of Biological Chemistry, Vol.288, pp.915-926
- Resource Type
- Journal article
- Publisher
- Elsevier Inc.; United States
- Series
- 288
- Copyright
- This is an Open Access article under the CC BY license.
- Identifiers
- WOS:000313570300016; 99380090775506600
- Academic Unit
- Usha Kundu, MD College of Health; Movement Sciences and Health
- Language
- English