An inhibitory role for mitochondrial fusion in Parkin-mediated mitophagy

• Main Authors: Yuan-Ping Huang, 黃元平
• Other Authors: Wei-Yuan Yang
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/3z6z72

博士 === 國立臺灣大學 === 生化科學研究所 === 106 === It has been found that autophagy is a key determinant for the life span of mitochondria through a particularly fine-tuned mechanism called mitophagy. Cells need to ensure their mitochondrial quality to remain viable. This is achieved in part by the selective degradation of damaged mitochondria through a well-characterized pathway termed PINK/Parkin-mediated mitophagy. We have now identified mitochondrial dynamics as an additional means for mitochondrial quality control: fusion of a functionally-impaired mitochondrion with the nearby mitochondrial network can promote the recovery of its function. The discovery was made possible through the use of a photosensitizer to functionally disturb mitochondria. Here we used photosensitizers to damage selected mitochondria and traced their fate with PAGFP, a photoactivatable fluorescent protein. Perturbing mitochondrial dynamics through siRNA like TRAK1, Miro1 and Miro2, the enzyme O-GlcNAc Transferase (OGT), whose activity depends on glucose availability, led to alteration in the likely-hood of impaired mitochondria to undergo mitophagy. We found that fusion with nearby mitochondrial network can promote the recovery of a damaged mitochondrion’s function. We investigated on the molecular mechanisms and roles of mitochondrial fission/fusion and mitochondrial motility in mitophagy. These results suggest coordination between mitochondrial dynamics and mitophagy in maintaining mitochondrial quality.