Researcher Studies Role of Copper in Muscle Development

Copper is essential for many key bodily processes—breathing, forming red blood cells and collagen, and keeping the immune system healthy. The body only requires trace amounts of the mineral in its cells, but an imbalance of copper can lead to serious neurological, cognitive, and muscular disorders, according to a recent paper published in the Public Library of Science (PLOS) by Assistant Professor of Molecular Biology and Biochemistry Teresita (Tere) Padilla-Benavides and co-authors.

Researchers have identified a copper-binding protein, mCrip2, that plays an important role in skeletal muscle growth regulation and maintaining homeostasis in muscular cells. The research expands the understanding of the copper network in precursor muscular cells, the paper said.

“We found that myoblast skeletal muscle cells, the precursor stem cells that make muscle in vitro, cannot make muscle without this protein,” Padilla-Benavides said.

First, researchers used a technique—known as synchrotron X-ray fluorescence-mass spectrometry—to study trace amounts of elements in biological samples, to identify the mCrip2 protein. Then, to determine the impact mCrip2 has on muscle regulation, researchers deleted the protein using the gene-editing technology CRISPR/Cas9. The team found that removing the protein disrupted muscle formation by an accumulation of copper in cells. Further analysis of the protein found that it regulates the expression of certain genes involved in muscular growth and homeostasis.

Padilla-Benavides was also recently involved in another copper-related study looking into the element’s impact on certain cancer cells. The research team published their research in the Proceedings of the National Academy of Sciences (PNAS) on Jan. 15. In this paper, researchers outlined a strategy that enabled them to profile the proportion of copper the body is able to absorb across many types of cells. With this strategy, they found certain cancer cells that are more susceptible to cell death through manipulation of copper levels, known as induced copper chelation.

Much of the research surrounding copper in biology is related to its role in cellular homeostasis, but more recent work in the field has pointed to copper as a necessary factor in the development and function of cell and tissue types, as she outlined in a paper in Metallomics in October 2024. Padilla-Benavides’s lab studies the biological roles of transition metals, like copper, zinc, cobalt, and manganese, in the development of mammalian cells. These metals play a critical role in biology and have an impact on processes like energy production, tissue generation, and stress response.

“I’m trying to understand how unknown players, like this protein mCrip2 and others we are studying, contribute to maintenance of cellular homeostasis to establish proper physiological phenotypes and how alterations in metal balance leads to disease,” Padilla-Benavides said. There is not a known disease tied to Crip2 at this stage, but there are disorders like Menkes and Wilson’s disease related to copper-imbalance. From here, the lab has begun to further research the Crip2 protein in mice models, with the hope of characterizing the mechanisms by which this protein, and other novel copper-binding proteins that they have identified, contribute to the deleterious phenotypes observed in Wilson’s and Menkes patients.