TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis.

Autor:	Ma X; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Rawnsley DR; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Kovacs A; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Islam M; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Murphy JT; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Zhao C; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Kumari M; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Foroughi L; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Liu H; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Qi K; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Diwan A; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Hyrc K; Alafi Neuroimaging Laboratory, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA., Evans S; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Satoh T; Department of Immune Regulation, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., French BA; Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA., Margulies KB; Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Javaheri A; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA., Razani B; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Mann DL; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA., Mani K; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA., Diwan A; Center for Cardiovascular Research and Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.; John Cochran VA Medical Center, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	JACC. Basic to translational science [JACC Basic Transl Sci] 2021 Dec 17; Vol. 7 (3), pp. 223-243. Date of Electronic Publication: 2021 Dec 17 (Print Publication: 2022).
DOI:	10.1016/j.jacbts.2021.12.002
Abstrakt:	Mitochondria are essential for cardiac myocyte function, but damaged mitochondria trigger cardiac myocyte death. Although mitophagy, a lysosomal degradative pathway to remove damaged mitochondria, is robustly active in cardiac myocytes in the unstressed heart, its mechanisms and physiological role remain poorly defined. We discovered a critical role for TRAF2, an innate immunity effector protein with E3 ubiquitin ligase activity, in facilitating physiological cardiac myocyte mitophagy in the adult heart, to prevent inflammation and cell death, and maintain myocardial homeostasis. Competing Interests: This study was supported by National Institutes of Health (NIH) grant HL107594 and by the Hope Center Viral Vectors Core at Washington University School of Medicine. Experiments were performed in part through the use of Washington University Center for Cellular Imaging supported by Washington University School of Medicine, The Children’s Discovery Institute of Washington University, and St. Louis Children’s Hospital grants CDI-CORE-2015-505 and CDI-CORE-2019-813; and the Foundation for Barnes-Jewish Hospital grants 3770 and 4642. Dr Rawnsley is supported by NIH grant T32 HL007081. Dr Javaheri is supported by NIH grants K08HL138262 and 1R01HL155344; by the Children's Discovery Institute of Washington University (MC-FR-2020-919) and St. Louis Children's Hospital, as well as the Diabetes Research Center grant P30DK020579; and the Nutrition Obesity Research Center at Washington University grant P30DK056341. Dr Mani was supported by a Seed Grant from the St. Louis VA Medical Center and by a Pilot and Feasibility grant from the Diabetes Research Center at Washington University (NIDDK grant No. P30 DK020579). Dr Abhinav Diwan is supported by NIH grants HL143431 and NS094692, and the Department of Veterans Affairs grant I01BX004235. Dr Mani serves as a member of the Cardiovascular Scientific Advisory Board at Dewpoint Therapeutics. Dr Abhinav Diwan provides consulting services to ERT systems for interpretation of echocardiograms in clinical trials; and serves as a member of the Cardiovascular Scientific Advisory Board at Dewpoint Therapeutics. These interests are not related to and did not influence the current study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Databáze:	MEDLINE
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