Document Detail

PTEN-inducible kinase 1 (PINK1)/Park6 is indispensable for normal heart function.
MedLine Citation:
PMID:  21606348     Owner:  NLM     Status:  MEDLINE    
Oxidative stress is caused by an imbalance between reactive oxygen species (ROS) production and the ability of an organism to eliminate these toxic intermediates. Mutations in PTEN-inducible kinase 1 (PINK1) link mitochondrial dysfunction, increased sensitivity to ROS, and apoptosis in Parkinson's disease. Whereas PINK1 has been linked to the regulation of oxidative stress, the exact mechanism by which this occurs has remained elusive. Oxidative stress with associated mitochondrial dysfunction leads to cardiac dysfunction and heart failure (HF). We hypothesized that loss of PINK1 in the heart would have deleterious consequences on mitochondrial function. Here, we observed that PINK1 protein levels are markedly reduced in end-stage human HF. We also report that PINK1 localizes exclusively to the mitochondria. PINK1(-/-) mice develop left ventricular dysfunction and evidence of pathological cardiac hypertrophy as early as 2 mo of age. Of note, PINK1(-/-) mice have greater levels of oxidative stress and impaired mitochondrial function. There were also higher degrees of fibrosis, cardiomyocyte apoptosis, and a reciprocal reduction in capillary density associated with this baseline cardiac phenotype. Collectively, our in vivo data demonstrate that PINK1 activity is crucial for postnatal myocardial development, through its role in maintaining mitochondrial function, and redox homeostasis in cardiomyocytes. In conclusion, PINK1 possesses a distinct, nonredundant function in the surveillance and maintenance of cardiac tissue homeostasis.
Filio Billia; Ludger Hauck; Filip Konecny; Vivek Rao; Jie Shen; Tak Wah Mak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-23
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-09     Completed Date:  2011-08-26     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9572-7     Citation Subset:  IM    
Campbell Family Cancer Research Institute, Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9.
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MeSH Terms
Animals, Newborn
Blotting, Western
Cardiomegaly / enzymology,  genetics,  pathology
Cells, Cultured
Heart Failure / enzymology*,  genetics,  pathology
Membrane Potential, Mitochondrial
Mice, Knockout
Microscopy, Fluorescence
Middle Aged
Myocardium / enzymology*,  metabolism
Myocytes, Cardiac / metabolism
Protein Kinases / genetics,  metabolism*
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Ventricular Dysfunction, Left / enzymology,  genetics,  pathology
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
EC 2.7.-/Protein Kinases; EC putative kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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