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Rab9-dependent autophagy is required for the IGF-IIR triggering mitophagy to eliminate damaged mitochondria.

Research paper by Chih-Yang CY Huang, Wei-Wen WW Kuo, Tsung-Jung TJ Ho, Shu-Fen SF Chiang, Pei-Ying PY Pai, Jing-Ying JY Lin, Ding-Yu DY Lin, Chia-Hua CH Kuo, Chih-Yang CY Huang

Indexed on: 27 Mar '18Published on: 27 Mar '18Published in: Journal of Cellular Physiology



Abstract

Mitochondria dysfunction is the major characteristic of mitophagy, which is essential in mitochondrial quality control. However, excessive mitophagy contributes to cell death in a number of diseases, including ischemic stroke and hepatotoxicity. Insulin-like growth factor II (IGF-II) and its receptor (IGF-IIR) play vital roles in the development of heart failure during hypertension. We found that IGF-II triggers IGF-IIR receptor activation, causing mitochondria dysfunction, resulting in mitophagy, and cardiomyocyte cell death. These results indicated that IGF-IIR activation triggers mitochondria fragmentation, leading to autophagosome formation, and loss of mitochondria content. These results are associated with Parkin-dependent mitophagy. Additionally, autophagic proteins Atg5, and Atg7 deficiency did not suppress IGF-IIR-induced mitophagy. However, Rab9 knockdown reduced mitophagy and maintained mitochondrial function. These constitutive mitophagies through IGF-IIR activation trigger mitochondria loss and mitochondrial ROS accumulation for cardiomyocyte viability decrease. Together, our results indicate that IGF-IIR predominantly induces mitophagy through the Rab9-dependent alternative autophagy. © 2018 Wiley Periodicals, Inc.

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