Figure 3
Integrating mitophagy and the UPR mt . While mitochondria are dynamic, at a given point in time they form a pool of at least semi-independent cellular compartments. Because PINK1 specifically accumulates on individual defective organelles (red), the mitophagy pathway is well equipped to monitor the health of individual organelles. On the other hand, ATFS-1 accumulates in the cytosol in proportion to the total amount of cellular mitochondrial stress. Because mitochondrial protein import is post-translational, ATFS-1 can accumulate in the cytosol during conditions where multiple individual mitochondria are severely defective (red; middle panel), or if the total pool of organelles is modestly stressed (far right panel). ATFS-1 induces transcription of a number of genes whose protein products must be imported into mitochondria to promote their recovery. Because the healthiest organelles are the most import competent, the UPRmt likely promotes the recovery of those organelles that can be salvaged. Concomitantly, by culling the most defective organelles, PINK1-dependent mitophagy enriches the healthy pool of organelles, allowing the resources required for mitochondrial repair to be allocated to the salvageable mitochondrial population.