Fighting cell death with sulfur

Antioxidants are well covered in advertising. They protect cells by neutralizing free radicals before these can cause cellular damage. While some antioxidants, such as certain vitamins, are obtained through the diet, the body can produce its own antioxidants.

An international team from the Max Planck Institute and Tohoku University in Sendai has now shown for the first time that mammalian cells produce and store elemental sulfur in a controlled manner in the form of cyclooctasulfur (S₈). This molecule, which consists of eight sulfur atoms, serves as a precursor for an endogenous antioxidant.

Antioxidants such as vitamins C and E protect cells by neutralizing free radicals, such as reactive oxygen species, before these can damage genetic material or cell membranes. Such damage can contribute to the development of neurodegenerative diseases. Antioxidants therefore help to prevent cellular damage.

Antioxidants are not obtained exclusively through the diet, as the body can also synthesize them with the help of various enzymes. An international research team led by Professor Takaaki Akaike of Tohoku University in Sendai and Dr. Uladzimir Barayeu, Research Group Leader at the Max Planck Institute for Polymer Research in Mainz, has now demonstrated a new mechanism that contributes to the body's own production of antioxidants. The researchers showed that mammalian cells produce and store elemental sulfur in a controlled manner in the form of cyclooctasulfur, a molecule consisting of eight sulfur atoms.

At the heart of this protective system is the enzyme eNOS, which is found in many cells. It produces nitric oxide, a molecule that relaxes blood vessels and thereby regulates blood pressure. The researchers have now shown for the first time that eNOS has another function: the enzyme produces cyclooctasulfur, which serves as a storage form of elemental sulfur in cells.

The researchers found particularly high concentrations of these "sulfur rings" in the oxygen-dependent mitochondria, the powerhouses of the cell, as well as in lipid droplets, which serve as the cell's fat stores. Through chemical reactions, the body can use its supply of S₈ molecules to produce specialized sulfur compounds known as hydropersulfides, which act as antioxidants.

Sulfur was an important component of the metabolism of many early forms of life. Since mitochondria evolved from bacteria, the presence of S₈ within them may point to an ancient biochemical legacy. The international team's findings thus reveal for the first time a surprising link between primordial sulfur chemistry and modern, oxygen-respiring mammalian cells.

The study, published in Science, opens up a fundamentally new perspective on cells' internal antioxidant defenses. In the long term, this knowledge could open up new avenues for understanding diseases such as neurodegenerative disorders more fully and treating them more precisely. However, further research will be needed before these findings can be translated into medical applications.

» Original publication

Source: Max Planck Institute for Polymer Research (MPI-P)