mitochondrial toxicity

Mitochondria are the tiny power plants inside nearly every cell, turning food and oxygen into usable energy. Mitochondrial toxicity is drug-induced damage to these power plants, so cells can no longer make enough energy. Tissues that burn the most fuel, such as the heart, liver, muscle, and nerves, suffer first.

Drugs can sabotage mitochondria in several ways: by jamming the electron-transport chain that generates energy, by uncoupling that chain so it wastes fuel as heat, or by interfering with the mitochondria's own DNA. The result is a drop in ATP production and often a surge of damaging reactive oxygen species, which can ultimately push cells toward death.

Mitochondrial injury is a frequently overlooked contributor to drug-induced liver and heart toxicity, and it can be slow and subtle, accumulating before it becomes obvious. Because standard cell assays grown in sugar-rich media can mask it, discovery teams use specialized tests (for example, forcing cells to rely on mitochondria by switching them to galactose) to expose hidden mitochondrial liabilities.