TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis
Xiucui Ma, David R. Rawnsley, Attila Kovács, Moydul Islam, John T. Murphy, Chen Zhao, Minu Kumari, Layla Foroughi, Haiyan Liu, Kevin Qi, Aaradhya Diwan, Krzysztof Hyrc, Sarah Evans, Takashi Satoh, Brent A. French, Kenneth B. Margulies, Ali Javaheri, Babak Razani, Douglas L. Mann, Kartik Mani, Abhinav Diwan
Abstract
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.