The lab of Li Yu has now identified a new cellular mechanism to eliminate damaged mitochondria, which they term mitocytosis (Jiao, H. Cell 184, 2896–2910.e13 (2021)). This process requires migrasomes, organelles of migrating cells that break off from retraction fibers at the rear of the cells.
The authors first observe that damaged mitochondria locate to migrasomes—in the cell in the figure, mitochondria (labeled in yellow) can be observed inside migrasomes (labeled in cyan) at the tips of the retraction fibers. This relocalization is induced by treatment with a wide array of mitochondrial stressors. They next investigate the dynamics of mitocytosis, observing that the damaged mitochondria, when close to the plasma membrane, adhere to it and become ‘trapped’ there. Subsequently, they move into the retraction fibers and then the migrasomes, to be discarded. This migration is dependent on the microtubule-dependent outward motor kinesin KIF5B, which pulls the mitochondria to the plasma membrane. There, the actin-based motor molecule Myo19, which localizes to the mitochondrial outer membrane, tethers the damaged mitochondria to cortical actin associated with the plasma membrane. Additionally, Drp1, a mitochondrial fission factor, is required for the mitochondrial tips to bind to cortical actin and for mitochondria to undergo fission and to be loaded into the migrasomes. The authors also find that, as compared to mitochondria that were not exposed to stressors, compromised mitochondria have reduced affinity for the inward motor dynein and increased affinity for KIF5B and, therefore, are preferentially transported to the periphery.
This is a preview of subscription content, access via your institution