Controlling energy production by calcium is an organ-specific affair

Now, researchers at Thomas Jefferson University have shown that the composition of the mitochondrial calcium portal (the protein that regulates when and how much calcium enters) is different depending on the organ in the body, and this difference allows mitochondria to tune their energy output by decoding a pattern of amplitude and/or frequency of calcium oscillations inside a cell. The results, published March 7 in the journal Cell Reports, could shed light on our basic understanding of organ health and disease.

“The mitochondria have to adjust the energy production to meet the metabolic needs of the tissue, whether it’s in the heart, the liver, or the muscle,” says Gyorgy Hajnoczky, M.D., Ph.D., the Raphael Rubin Endowed Chair and Professor of Pathology, Anatomy and Cell Biology at Thomas Jefferson University and Director of the Jefferson MitoCare Center.

Dr. Hajnoczky and colleagues Gyorgy Csordas, M.D. and Erin Seifert, Ph.D., faculty at the MitoCare Center, looked at the composition of the mitochondrial calcium portal in three tissue types of mice: heart, liver and skeletal muscle, and noticed that the ratio of the main channel protein, called MCU, and a regulator protein, called MICU1, varied across tissue types. They and others had previously shown that MICU1 is a calcium sensing master switch that both seals the channel until a threshold is reached then expedites its activation.

Strikingly, the group found that the liver contained a high amount of the regulator protein relative to the amount of the channel protein, whereas the heart had a lower ratio of regulator protein. This meant that liver cells have mitochondrial calcium channels that are more likely to be under the control of the regulator, while heart cells have less guarded mitochondrial calcium channels.

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