Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
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.