Journal article
MICAL1 constrains cardiac stress responses and protects against disease by oxidizing CaMKII
The Journal of clinical investigation, Vol.130(9), pp.4663-4678
09/01/2020
DOI: 10.1172/JCI133181
PMCID: PMC7456244
PMID: 32749237
Abstract
Oxidant stress can contribute to health and disease. Here we show that invertebrates and vertebrates share a common stereospecific redox pathway that protects against pathological responses to stress, at the cost of reduced physiological performance, by constraining Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity. MICAL1, a methionine monooxygenase thought to exclusively target actin, and MSRB, a methionine reductase, control the stereospecific redox status of M308, a highly conserved residue in the calmodulin-binding (CaM-binding) domain of CaMKII. Oxidized or mutant M308 (M308V) decreased CaM binding and CaMKII activity, while absence of MICAL1 in mice caused cardiac arrhythmias and premature death due to CaMKII hyperactivation. Mimicking the effects of M308 oxidation decreased fight-or-flight responses in mice, strikingly impaired heart function in Drosophila melanogaster, and caused disease protection in human induced pluripotent stem cell-derived cardiomyocytes with catecholaminergic polymorphic ventricular tachycardia, a CaMKII-sensitive genetic arrhythmia syndrome. Our studies identify a stereospecific redox pathway that regulates cardiac physiological and pathological responses to stress across species.
Details
- Title: Subtitle
- MICAL1 constrains cardiac stress responses and protects against disease by oxidizing CaMKII
- Creators
- Klitos Konstantinidis - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAVassilios J Bezzerides - Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USALo Lai - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USAHolly M Isbell - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAAn-Chi Wei - Department of Electrical Engineering, Graduate Institute of Biomedical and Bioinformatics, National Taiwan University, Taipei City, TaiwanYuejin Wu - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAMeera C Viswanathan - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAIan D Blum - Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USAJonathan M Granger - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USADanielle Heims-Waldron - Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USADonghui Zhang - State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Science, Hubei University, Wuhan, ChinaElizabeth D Luczak - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAKevin R Murphy - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAFujian Lu - Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USADaniel H Gratz - Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USABruno Manta - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USAQiang Wang - Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, ChinaQinchuan Wang - Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USAAlex L Kolodkin - Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Maryland, USAVadim N Gladyshev - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USAThomas J Hund - Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, Ohio, USAWilliam T Pu - Harvard Stem Cell Institute, Cambridge, Massachusetts, USAMark N Wu - Department of Genetic MedicineAnthony Cammarato - Department of Physiology, andMario A Bianchet - Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, Maryland, USAMadeline A Shea - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USARodney L Levine - Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USAMark E Anderson - Department of Physiology, and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.130(9), pp.4663-4678
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI133181
- PMID
- 32749237
- PMCID
- PMC7456244
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- R01 GM065204 / NIGMS NIH HHS\r\nR01 NS079584 / NINDS NIH HHS\r\nR01 HL134824 / NHLBI NIH HHS\r\nR01 AG021518 / NIA NIH HHS\r\nR35 HL140034 / NHLBI NIH HHS\r\nS10 OD025244 / NIH HHS\r\nR01 HL135096 / NHLBI NIH HHS\r\nT32 HL007227 / NHLBI NIH HHS\r\nR01 HL124091 / NHLBI NIH HHS\r\nR37 GM065204 / NIGMS NIH HHS\r\nR21 NS108842 / NINDS NIH HHS\r\nZIA HL000225 / Intramural NIH HHS\r\nR01 GM057001 / NIGMS NIH HHS
- Language
- English
- Date published
- 09/01/2020
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology
- Record Identifier
- 9984070681802771
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