How Mitochondria Prevent Spread of Heart or Skeletal Muscle Damage

Heart mitochondria build power grid networks in a way that allows them to confine disturbances in energy flow to a small region, preventing damage to an entire muscle.

The insight may help scientists further understand heart and skeletal muscle function in conditions ranging from heart to mitochondrial disease. Mitochondria, known as the cells’ powerhouses, transform food into energy.

A research team at the National Heart, Lung, and Blood Institute discovered that the body’s power grid networks are organized in smaller sub-networks, with a circuit breaker that can bypass a damaged area.

The study, “Power Grid Protection of the Muscle Mitochondrial Reticulum,” was published in the journal Cell Reports.

The findings built on research published in 2015 showing that mitochondria in skeletal muscle were connected in a power-grid type of network. Researchers wondered what would happen to the grid if part of it — one chunk of mitochondria — was damaged.

Advanced three-dimensional imaging allowed the team to explore the issue in skeletal and heart muscle cells. They discovered that, in the heart, the power grid is divided into sub-sections organized in parallel rows.

When part of the grid is damaged, the problem is confined to a sub-section.

In a press release, the team compared the scenario to that seen when lightning strikes a city power grid. “Lights may flicker over the whole city, but once the circuit breaker activates, only part of the city loses power,” they wrote.

Both heart and skeletal muscle mitochondria have other ways to protect the grid as well. When one part is damaged, healthy mitochondria rapidly close the connection to the damaged part. In fact, the  connection — called an intermitochondrial junction — is closed within seconds of an injury appearing.

The closure prevents electrical signals from traveling between mitochondria, so the damaged region can recover.

If the damage lasts, healthy mitochondria physically separate from damaged ones. Meanwhile, the injured energy-makers change their shape from the elongated form seen in the networks to a smaller condensed structure.

The study shows that heart mitochondria have both proactive and reactive mechanisms to protect the power grid, researchers said. Since the consequences of damage to heart mitochondria is more far-reaching than a skeletal muscle injury, the extra level of protection in the heart ensures that damage to a small region does not impact the entire heart muscle.