Powering Up Muscle

Image credit: Veronica Falconieri, National Cancer Institute

Because of their special function – spending energy to generate large-scale movement – skeletal muscle cells need a unique solution for how to manage energy. The biggest challenge is carrying that energy from capillaries, where oxygenated blood delivers fresh oxygen to the muscle cells, deep into the tissue.

Mitochondria, cellular “power houses”, use oxygen and water to convert energy into a form the cell can use. The conversion process first moves protons (H+) across the inner membrane of the mitochondria, creating an electrical potential, or “gradient”. This gradient then drives protons back through a molecular rotor that uses the energy to charge up molecules of ADP and form ATP. ATP is a critical energy source for the majority of cellular functions – including muscle contraction.

In a collaborative study with Dr. Balaban’s group at NHLBI that we published in Nature in 2015, we used focused ion beam scanning electron microscopy (FIB-SEM) to visualize a continuous network of mitochondria extending from the capillary into the muscle tissue. This work showed that the electrical gradient extends directly through the mitochondrial network, allowing the cell to transfer energy through the network. The cell can then generate most of its ATP at the location where it’s needed, rather than laboriously transporting ATP molecules from the capillary area into the deep areas of the muscle tissue.

In a followup study published in Cell Reports in 2017, we found that mitochondrial networks in the heart muscle are smaller. This means that injury to one area of the network won’t carry over into neighboring areas of the heart, offering protection against cascading damage to this critical organ.

The illustration above depicts a cross-section (middle) of a skeletal muscle fiber (left). Mitochondria (blue) are clustered around a capillary (magenta); the mitochondrial network extends between the myofibrils (red). In a zoomed-in view of the mitochondrial network (right), the proton gradient is generated near the capillary (where the oxygen level is high), then the proton gradient drives ATP production far from the capillary (where the oxygen level is low).

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Related References: Glancy B, Hartnell LM, Malide D, Yu ZX, Combs CA, Connelly PS, Subramaniam S, and Balaban RS. Mitochondrial reticulum for cellular energy distribution in muscle. Nature. 2015 July 30;523:617-20. doi: 10.1038/nature14614. [PubMed]

Glancy B, Hartnell LM, Combs CA, Fenmou A, Sun J, Murphy E, Subramaniam S, and Balaban RS. Power Grid Protection of the Muscle Mitochondrial Reticulum. Cell Rep. 2017 Apr 18;19(3):487-496. doi: 10.1016/j.celrep.2017.03.063. [PubMed]