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Andrew Brennan Last Updated:Monday, September 26, 2016

Role of Calcium & Magnesium in Cell Regulation

There is an increasing realisation from the scientific community of the synergistic relationship between calcium and magnesium. The article below from Science Daily highlights a groundbreaking new study that shows the importance of both calcium and magnesium ions in effective cell regulation.

From ScienceDaily:

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Recent work published in the Journal of Cell Chemical Biology has shed light on the importance of calcium and magnesium in cell regulation.

Mitochondria in each cell are responsible for generating energy to ensure cell function. A membrane within the mitochondria is responsible for intracellular regulation of calcium ions, the Ca2+ uniporter (MCU). The recent discover of a key MCU domain has shown that both calcium and magnesium ions play a role in both the energy required for cell function and of cell death.

The research was conducted by Muniswamy Madesh, Ph.D., Professor in the Center for Translational Medicine and the Department of Medical Genetics and Molecular Biochemistry at the Lewis Katz School of Medicine Temple University.

Dr Madesh explained in the Science Daily article that “Calcium is a key regulator of energy production in mitochondria, but too much of it can trigger cell death,” MCU activity is vital to calcium homeostasis and cell survival. “But if the pore fails to close,” Dr. Madesh explained, “mitochondria retain the energy they synthesize in the form of ATP. The resulting accumulation of oxidants and calcium overload lead to mitochondrial swelling and cell stress.”

Insight into MCU structure could help researchers find ways to modulate the gateway’s activity and potentially restore its function in disease states including various cardiovascular and neurological conditions.

In the new study, Dr. Madesh and colleagues describe the atomic structure of the MCU N-terminal domain and report the discovery of a “grasp” region of the domain dedicated specifically to the binding of calcium and magnesium ions. They found that interaction of the ions with the region destabilizes the MCU channel, causing the gateway to close.

In experiments in human cells, mutations introduced into the grasp region disrupted MCU assembly and greatly attenuated mitochondrial calcium uptake through the channel. The researchers further discovered that MCU activity could be blocked both by bathing mitochondria in magnesium and by preventing mitochondrial calcium displacement. The discovery supports previous studies, suggesting that MCU is autoregulated via a mechanism involving either calcium-dependent inactivation or magnesium-induced inhibition.

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According to Dr. Madesh, the new structural and mechanistic insights from his team’s study help fill in gaps in scientists’ understanding of the role of MCU in controlling mitochondrial calcium uptake. The new findings also have important implications for the understanding of diseases involving mitochondrial dysfunction.

Click here for a link to the original article:

Journal Reference:
Samuel K. Lee et al. Structural Insights into Mitochondrial Calcium Uniporter Regulation by Divalent Cations. Cell Chemical Biology, August 2016 DOI: 10.1016/j.chembiol.2016.07.012

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