Journal article
TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis
JACC. Basic to translational science, Vol.7(3), pp.223-243
03/01/2022
DOI: 10.1016/j.jacbts.2021.12.002
PMCID: PMC8993766
PMID: 35411325
Abstract
[Display omitted]
•TRAF2, an innate immunity adaptor protein, localizes to the mitochondria in cardiac myocytes in human and mouse hearts during physiology, with increased mitochondrial localization under pathologic stress.•TRAF2 is essential for physiological mitophagy in cardiac myocytes, with a critical requirement for its E3 ligase domain in this role.•TRAF2 suppresses expression of TLR9, a sensor for leaked mitochondrial DNA, to suppress sterile inflammation in the myocardium.•Loss of physiological TRAF2-mediated mitophagy in cardiac myocytes triggers myocardial inflammation and cardiac myocyte cell death. Interruption of TLR9-mediated mitochondrial DNA sensing rescues inflammation, but persistence of damaged mitochondria leads to cell death with aging, pointing to a critical role for physiological cardiac myocyte mitophagy in maintaining myocardial homeostasis.
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.
Details
- Title: Subtitle
- TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis
- Creators
- Xiucui Ma - Washington University in St. LouisDavid R. Rawnsley - Washington University in St. LouisAttila Kovacs - Washington University in St. LouisMoydul Islam - Washington University in St. LouisJohn T. Murphy - Washington University in St. LouisChen Zhao - Washington University in St. LouisMinu Kumari - Washington University in St. LouisLayla Foroughi - Washington University in St. LouisHaiyan Liu - Washington University in St. LouisKevin Qi - Washington University in St. LouisAaradhya Diwan - Washington University in St. LouisKrzysztof Hyrc - Washington University in St. LouisSarah Evans - Washington University in St. LouisTakashi Satoh - The University of TokyoBrent A. French - University of VirginiaKenneth B. Margulies - University of PennsylvaniaAli Javaheri - Washington University in St. LouisBabak Razani - Washington University in St. LouisDouglas L. Mann - Washington University in St. LouisKartik Mani - Washington University in St. LouisAbhinav Diwan - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- JACC. Basic to translational science, Vol.7(3), pp.223-243
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jacbts.2021.12.002
- PMID
- 35411325
- PMCID
- PMC8993766
- ISSN
- 2452-302X
- eISSN
- 2452-302X
- Language
- English
- Date published
- 03/01/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695827302771
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