To generate energy, mitochondria manipulate sugars. First, a cell breaks apart glucose into a smaller molecule called pyruvate, which the cell then imports intoa mitochondrion. Via a multistep process, the mitochondrion strips each pyruvate molecule of its carbon atoms to create two other molecules, reduced nicotinamide adenine dinucleotide (NADH) and 1,5-dihydroflavin adenine dinucleotide (FADH2). Machinery within the mitochondria, the electron transport chain, extracts electrons from NADH and FADH2 and pumps positively charged protons into the intermembrane space (mitochondria have two cell membranes). The protons are then drawn back inward to the negatively charged mitochondrial matrix at the mitochondrion’s center, and as they surge across the membrane, they turn a waterwheel-like molecule, adenosine triphosphate (ATP) synthase. That generates energy, which is stored in ATP and used by every cell and organ in the body.

Mitochondria’s 37 genes code for the manufacture of key proteins and helper molecules in the energy production pathway (including the electron transport chain) and are all inherited from the mother’s mitochondria-packed egg. In 1981 Nobel laureate Frederick Sanger and his colleagues in Cambridge, England, determined the sequence of these genes. That enabled researchers to compare mitochondrial DNA in healthy people with that in patients suffering from a number of rare, maternally inherited diseases. Scientists eventually discovered 50 mutations and linked them to a series of devastating disorders known by such acronyms as MELAS, LHON and MERRF. In all these diseases, the genetic mutations have crippled the mitochondria’s energy-producing machinery.

Intriguing findings in small studies of humans and in animal research have since directed scientists toward a closer examination of mitochondria’s involvement in other, more complex diseases—those with multiple genetic and environmental causes, including Parkinson’s, type 2 diabetes and cancer. The researchers suspected that smaller mutations in a series of nuclear genes that encode mitochondrial proteins, or slight mitochondrial defects stemming from environmental factors or even simple aging, could help trigger these diseases. Disabled mitochondria do a poor job producing energy, and that allows electrons to leak out of the electron transport chain and interact with oxygen inside the mitochondria, creating free radicals that further damage the mitochondria. Some mitochondria in a cell may completely shut down, while others function so poorly that they trigger a chain reaction of destructive events. The diseases that may result from this dimming and flickering are less immediately severe than those that are caused by mutations in mitochondrial DNA, but they may end up being just as deadly.

The link between mitochondria and Parkinson’s disease was discovered serendipitously in the early 1980s, when addicts began injecting a contaminated version of a euphoria-inducing drug called meperidine. In fact, the drug had been inadvertently poisoned by a meperidine by-product called MPTP. After the drug users developed symptoms strikingly similar to those of late-stage Parkinson’s, researchers found that MPTP inhibits mitochondria’s energy-producing machinery in neurons that make dopamine—the same neurons that are killed in Parkinson’s disease.

Since then, researchers have identified at least three nuclear genes whose proteins are associated with mitochondria. Preliminary evidence suggests that these genes are all involved in managing oxidative stress—the damage caused by free radicals. This points to a possible vicious cycle of deterioration in which mutations hinder the mitochondrion’s ability to generate energy while churning out higher levels of polluting ROS, which, in turn, tear up a cell’s protective membranes and further mutate mitochondrial DNA. The damaged mitochondria may create still more ROS, and the cycle continues.