ECM modulates the link between mitophagy regulation and apoptosis

• Main Authors: Choong,Huey Ching, 莊惠晴
• Other Authors: Chen, Chun Hong
• Format: Others
• Language: en_US
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/kz8h2f

碩士 === 國立清華大學 === 生物科技研究所 === 104 === Mitochondria play roles in the regulation of energy production and apoptosis. Mitochondrial fusion and fission are crucial processes in mitochondria homeostasis. During apoptosis and mitophagy, mitochondria undergo morphological changes, which include fission and clustering, but the link between mitophagy regulation and cellular apoptosis is unclear. The Enlargement and Clustering Mitochondria (ECM) gene encodes a protein that localizes to the mitochondria. In Drosophila cells, the overexpression of ECM increases the size and aggregation of mitochondria. To investigate the signaling pathways by which ECM induces changes in mitochondrial morphology, we identified the Buffy and ATG6 genes as extragenic suppressors of ECM gene function. Buffy functions as a pro-survival Bcl-2-like protein, and beclin1, the mammalian orthologue of ATG6, are required for autophagosome formation. The co-overexpression of Buffy and ATG6 ameliorated the effects of ECM overexpression on mitochondrial morphology. The effects of ECM overexpression were also reversed by the knockdown of Reaper, Grim, and Hid expression using gene-specific siRNA. Our results suggest that pro-survival signaling pathways involved in mitophagy regulation may suppress ECM gene function. Our findings provide important insight into the dynamic processes involved in mitochondria homeostasis, and may be useful for identifying molecular targets in the development of novel therapies for mitochondrial dysfunction-related conditions, including metabolism disorders and aging.