Complement Function Expands

Complement molecules are the immune proteins responsible for identifying bacteria, viruses, and other foreign invaders as they circulate through our bodies. Their function helps lymphocytes to locate and eliminate pathogens. A particular protein known as C3 has always had a lucrative role, but current research has provided significant insight.

C3 is a complement protein central to a specific immune reaction that the details surrounding its function have been undescribed. Researchers at the Lund University in Sweden have reported how C3 regulates autophagy, the underlying mechanism that controls a cell’s ability to break down their make-up. Occasionally, cells must eliminate their waste to make way for new structures.

Previously described, if autophagy processes are interrupted, disease can result. The C3 expression can correlate with type-2 diabetes and inflammation. This makes the work done by these researchers critical; allowing for potential new research to happen, avoiding the route to disease.

The work published in Cell Metabolism shows that human pancreatic islets express high levels of C3 in the cytosol; the material in the cytoplasm, excluding the contents of the various membranous organelles. Another protein known as CD59 is essential for enabling beta cells to secrete insulin. C3 was produced in large amounts of beta cells.

Researchers find that C3 protects beta cells under stresses caused by long-term high blood sugar levels that result in diabetes. The team utilized CRISPR Cas9, a genetic editing tool, to remove the genes responsible for expressing C3 from beta cells. They found that autophagy was altered and cells died as a result of the stresses. Additionally, the study finds C3 production in beta cells rises due to diabetes and inflammation.

The researchers suggest the C3 production here is to protect beta cells. “Autophagy relieves cellular stresses faced by beta cells during T2D and maintains cellular homeostasis,” the team reports.

Immunologist, Anna Blom reports that they have “revealed a previously undescribed intracellular function for C3, connecting the complement system directly to autophagy, with a broad potential importance in other diseases and cell types.”

"C3 is a very old protein from an evolutionary perspective, and we have now shown that it not only has a role in the relatively modern immune system in the blood but also within cells, where it is needed for one of the most fundamental cellular functions, autophagy. In all likelihood, this applies to many cell types and opens the way for new principles in the treatment of diseases such as type 2 diabetes and certain neurodegenerative diseases for which there is a need to protect cells from stress," shares Anna Blom.

Sources: Cell Metabolism, Science Daily, YouTube