{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:27:45Z","timestamp":1790954865071,"version":"4.1.0"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,6,7]]},"abstract":"<jats:p>\n                    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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice develop left ventricular dysfunction and evidence of pathological cardiac hypertrophy as early as 2 mo of age. Of note, PINK1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1106291108","type":"journal-article","created":{"date-parts":[[2011,5,24]],"date-time":"2011-05-24T00:31:06Z","timestamp":1306197066000},"page":"9572-9577","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":383,"title":["PTEN-inducible kinase 1 (PINK1)\/Park6 is indispensable for normal heart function"],"prefix":"10.1073","volume":"108","author":[{"given":"Filio","family":"Billia","sequence":"first","affiliation":[{"name":"Campbell Family Cancer Research Institute, Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9;"},{"name":"Division of Cardiology, University Health Network (UHN), Toronto, ON, Canada M5G 2C4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Hauck","sequence":"additional","affiliation":[{"name":"Campbell Family Cancer Research Institute, Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Konecny","sequence":"additional","affiliation":[{"name":"Toronto Medical Discovery Tower, University of Toronto, Toronto, ON, Canada M5G 2C4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Surgery, University Health Network, Toronto, ON, Canada M5G 2C4; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak Wah","family":"Mak","sequence":"additional","affiliation":[{"name":"Campbell Family Cancer Research Institute, Princess Margaret Hospital, Toronto, ON, Canada M5G 2M9;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,5,23]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.1.14"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.59.1.551"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096284"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70327-7"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709336105"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.02.018"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802076105"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2010.05.016"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.017"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/14.11.1493"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.10.014"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/44.1.148"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025448908694"},{"key":"e_1_3_3_14_2","first-page":"I19","article-title":"Alterations in the coronary circulation in hypertrophied ventricles","volume":"75","author":"Marcus ML","year":"1987","unstructured":"ML Marcus, et al., Alterations in the coronary circulation in hypertrophied ventricles. Circulation 75, I19\u2013I25 (1987).","journal-title":"Circulation"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.21.2.209"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000046452.67724.B8"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)48474-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1295-376"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1027383100936"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50343-X"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02190607"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00737.2006"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04779"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803998105"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1107-1227"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1427.032"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901104106"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805514200"},{"key":"e_1_3_3_29_2","first-page":"2758","article-title":"Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice","volume":"119","author":"Sundaresan NR","year":"2009","unstructured":"NR Sundaresan, et al., Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest 119, 2758\u20132771 (2009).","journal-title":"J Clin Invest"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702717104"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1106291108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T20:06:14Z","timestamp":1649793974000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1106291108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,23]]},"references-count":30,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2011,6,7]]}},"alternative-id":["10.1073\/pnas.1106291108"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1106291108","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,23]]},"assertion":[{"value":"2011-05-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}