Medical News Today: Insights into mitochondrial 'power grids' increase understanding of heart muscle

A new study reveals further insights into how electrical "power grids" of interconnected mitochondria inside heart muscle cells work. It shows that a cell's grid comprises several smaller subnetworks and a mechanism that acts in a similar way to a circuit breaker. These features allow the grid to continue supporting the cell by limiting the spread of local failures such as disease-related breakdown of individual mitochondria.
Researchers used high-resolution imaging to look at mitochondria in a single heart cell - the ones highlighted in red in this image were exposed to ultraviolet light.
Image: NHLBI

The study is the work of a team at the National Institutes of Health (NIH) in Bethesda, MD, and it is published in the journal Cell Reports.

Lead author Dr. Brian Glancy, of the Muscle Energetics Laboratory at NIH's National Heart, Lung, and Blood Institute (NHLBI), and colleagues believe that their findings give important clues on how healthy and diseased heart and skeletal muscle works.

Such knowledge, they say, could increase understanding of conditions such as mitochondrial diseases, heart disease, and muscular dystrophy.

Muscle cells must provide lots of energy to power movement of muscles that perform a range of functions, from moving the arms and legs to pumping the heart.

To supply this energy, muscle cells contain many tiny compartments, or organelles, called mitochondria, which scientists often describe as the "powerhouses" of cells.

Mitochondria form a cellular 'power grid'

Mitochondria are specialized organelles that convert sugars, fats, and other nutrients into energy-rich molecules - particularly one known as adenosine triphosphate (ATP).

Mitochondria have some unusual features. For example, they have two surrounding membranes and their own genetic code that is separate from that held in the DNA in the cell nucleus.

They also divide independently from the cell; their timing and rate of replication is not coupled to that of the cell.

To produce ATP, the mitochondria rely on their two membranes: an outer one that has holes large enough for ions to pass through, and an inner one that is less permeable.

These, and other differences between the two membranes, allow the mitochondria to sustain a difference in voltage across them that acts as a temporary store of energy (much like a battery) that is essential for the production of ATP, through a process called oxidative phosphorylation.

However, after using high-resolution 3-D images to examine mitochondria inside mouse skeletal muscle cells, the same NIH team reported a groundbreaking study, published in 2015, which turned some of the long-held opinions regarding mitochondria on their head: the chemical diffusion of ATP was not the only means of energy distribution in cells.

In that study, the team revealed that the electrical energy stored in the voltage across the two membranes of mitochondria was a primary source of energy in the cell and "the dominant pathway for skeletal muscle energy distribution." The study established the idea that the mitochondria act as a "power grid" inside the cell.

Mitochondrial power grid has inbuilt safety features

In the new study, Dr. Glancy and colleagues take the earlier findings further and show that the mitochondrial power grid has inbuilt safety features that allow the cell to continue working if a part of the grid develops a fault.

Again, with the help of high-resolution 3-D images and light-activated probes, and working with mouse heart muscle and skeletal muscle cells, the team discovered that the power grids inside these cells comprise subnetworks of mitochondria that are linked through "intermitochondrial junctions," which act in a similar fashion to circuit breakers.

The researchers found that this arrangement allows for faulty mitochondria to be "electrically separated from the network in seconds," thus ensuring the integrity of the overall grid so that it can continue to supply the cell with energy.

The researchers liken the process to that of the power grid of a city. When lightning strikes, the lights could flicker over the entire city for a second or two, but thanks to the arrangement of circuit breakers and subnetworks, the grid quickly recovers and the power loss is confined to a small part of the network. They conclude:

"This mitochondrial network protection system limits the propagation of local failures and allows for the quick recovery of undamaged mitochondria in order to sustain cellular function."

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