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The appended video shows mitophagy occurring in real time in mouse embryonic fibroblasts from a strain in which LC3, the hallmark of autophagy, has been tagged with the fluorescent label, GFP (Mizushima N. Methods Enzymol. 2009;452:13-23.). Green dots, representing autophagosomes, go yellow when co-localising with mitochondrial fragments (labeled red)

Quality matters – mitochondrial DNA quality control

Mitochondria are in a constant state of fission and fusion, leading to the maintenance of a healthy mitochondrial population within the cell. Mitophagy is a cellular process that recycles damaged mitochondria and is likely to be a key quality control mechanism for mitochondrial DNA. We know that mitochondrial dynamics help decide which mitochondria undergo mitophagy. Dysfunctional mitochondria are segregated by fission processes from the mitochondrial network, and are fragmented enough to be taken up through mitophagy for degradation in autophagosomes which then become autolysosomes. Understanding mitochondrial network dynamics is integral for identifying mechanisms behind this selective degradation. 

We have developed high throughput imaging techniques1 and a model in which fluorescent markers are targeted to mitochondria (DS-red) and autophagosomes (GFP)2.  We are using these to study mitophagy in (i) normal development of pre-implantation embryos, mitochondrial diseases associated with (ii) mitochondrial DNA mutations3 and (iii) excessive mitochondrial fragmentation2.  We are identifying pharmacological modulators of mitophagy to see if these can be used to treat patients with mitochondrial disease.