Reactive oxygen species (ROS) that arise from electron transport chain activity can be neutralized by oxidation of mitochondrial proteins and lipids. However, the way these oxidized macromolecules are removed from the mitochondria is not clear. McBride and colleagues now show that a subpopulation of mitochondria-derived vesicles (MDVs) that are generated in response to oxidative stress are delivered to lysosomes (Curr. Biol. doi:10.1016/j.cub.2011.11.057; 2012). These MDVs might therefore be an important transport intermediate for degrading oxidized mitochondrial proteins.

McBride and colleagues found that MDVs were generated in mammalian cell lines as an early response to oxidative stress. Most of these structures contained the mitochondrial outer membrane protein Tom20, but lacked inner-membrane proteins or matrix-associated proteins. MDV formation did not require the GTPase Drp1 or the autophagy protein ATG5, and the MDVs did not co-localize with autophagosome marker LC3. This indicates that MDV formation is independent of the mitochondrial fission or mitophagy machinery. The authors then traced the movement of these stress-induced MDVs and found that they were delivered to multivesicular bodies, which went on to fuse with lysosomes. Together, these data suggest the existence of a stress-induced mitochondria–lysosome transport pathway that might mediate removal of damaged mitochondrial proteins.