Mitochondria are essential cell components that become dysfunctional with age, a cause of a significant fraction of age-related degeneration. These organelles are descended from ancient symbiotic bacteria, and the herd of mitochondria in a cell is dynamic, fusing together, splitting apart, and passing around component parts. As mitochondria become worn and damaged, they are removed by the quality control process of mitophagy. This all works well in youth.
In the context of aging, a fair amount of evidence points to impaired mitochondrial fission as an important contributing cause of impaired mitophagy, which in turn leads to impaired mitochondrial function as damaged mitochondria accumulate, which in turn causes all sorts of issues. The issue in question here is the reduced generation of new blood vessels with age, an impairment that may be very significant, as it contributes to the decline of capillary networks throughout the body and reduced blood supply to energy-hungry organs such as muscles and the brain.
The protein Drp1 is best known to enable an orderly splitting, or fission, of mitochondria so that one becomes two and/or mitophagy, which is trimming off dysfunctional parts of existing mitochondria and helping eliminate mitochondria that are beyond repair. Researchers now have early evidence that when oxygen levels are low in common problems like heart disease and peripheral artery disease in the legs, Drp1 gets modified and a new job. It again promotes splitting, or fission, of the powerhouses but in this case, the magic is in generating a powerful signal, via creation of reactive oxygen species (ROS), that makes glycolysis happen. Ready energy like from glycolysis is needed for the cell proliferation, migration, and movement of angiogenesis, and the endothelial cells that line existing blood vessels take the lead in making new ones.
Hypoxia, like the heart muscle crying out for more oxygen, is the natural cue for angiogenesis. Vascular endothelial growth factor (VEGF), which does just what its name implies, outside the endothelial cell is naturally stimulated by hypoxia, then in turn activates NADPH oxidase, a family of enzymes that generate ROS - in this case the kind that enables cell signaling. ROS generated by the mitochondria in turn activates AMPK, an enzyme key to regulating energy levels in cells and known to use glucose to quickly generate sufficient energy to support important biological work like making new blood vessels.
When ROS from the mitochondria is blocked, angiogenesis produced by endothelial cells also is impaired. And it appears to be a two-way street because VEGF's ability to enable angiogenesis also is impaired, and mitochondrial ROS can activate NADPH oxidase ROS and vice versa. Together the result is sustained signaling. If you block mitochondrial ROS, the chain reaction is blocked.