How the Cell's Power Station Survives Attacks

Mitochondria, the power generators in our cells, are essential for life. When they are under attack—from poisons, environmental stress or genetic mutations—cells wrench these power stations apart, strip out the damaged pieces and reassemble them into usable mitochondria. Now, Reuben Shaw’s lab has uncovered an unexpected way in which cells trigger this critical response to threats, offering insight into disorders such as mitochondrial disease, cancer, diabetes and neurodegenerative diseases—particularly Parkinson’s disease, which is linked to dysfunctional mitochondria. The work was published January 15, 2016 in Science.

The team found that when cells are exposed to mitochondrial damage, a central cellular fuel gauge, the enzyme AMPK, sends an emergency alert to mitochondria instructing them to break apart into many tiny mitochondrial fragments. Drilling down further, the researchers found that AMPK actually acts on two areas of a mitochondrial receptor, called mitochondrial fission factor (MFF), to start the process. MFF calls over a protein, Drp1, that binds and wraps around the mitochondrion like a noose to twist and break it apart.

Interestingly, AMPK is activated by the widely used diabetes therapeutic metformin, as well as exercise and a restricted diet. The new findings suggest that some of the benefits from these therapies may result from their effects in promoting mitochondrial health.