A genetic approach reveals selective elimination of damaged mitochondria in healthy cells and tissue. Yun Qi^1*, Jahda Hill¹, Guofeng Zhang², Hong Xu¹. 1) GDBC, NHLBI, bethesda, MD; 2) NIBIB, bethesda, MD.

   Mitochondrial turnover has been postulated as a mechanism for mitochondrial quality control. However, it remains a question whether cells are indeed able to eliminate defective mitochondria selectively. Quantitative and live imaging assays are required to measure selective mitochondrial degradation and visualize this process in real time, while a genetic approach is essential to probe mitochondrial turnover in a physiological context. We expressed a toxic bacterial protein, PorB, to damage a subpopulation of total cellular mitochondria in cultured Drosophila cells and tissues. Damaged mitochondria concentrated with PorB were segregated from the mitochondrial network through a fission/fusion process and selectively removed by lysosomes probably through the autophagy pathway in otherwise healthy cells. We also demonstrated in our model that the Parkin-dependent degradation of damaged mitochondria in an animal tissue, the Drosophila flight muscle. Our work proves in principle that defective mitochondria are selectively removed in healthy cells, and also provides a novel genetic approach to monitor mitochondrial turnover and dissect the underlying mechanisms.