Editor: Aigerim Akhmetova
Author: Aldiyarbek Nurlan
Ferroptosis is a special type of cell death that is caused by an imbalance of oxidation within cells. Ferroptosis leads to changes in molecules in the cell membrane, called lipids, and can be caused by cysteine starvation. Cysteine is a type of amino acid that is one of the building blocks of proteins and is also used by the body for a variety of important physiological processes, including cell survival, regulation of redox reactions, and energy transfer. Because of its critical role in normal processes, cysteine is strictly regulated to prevent excess or insufficient amounts of the amino acid.
Several different types of cancer overexpress molecules that play an important role in the regulation of cysteine. This suggests that a decrease in cysteine levels may negatively affect the growth of cancer. In fact, studies have shown that cancer cells can be induced to kill cells either by inhibiting cysteine uptake or by starving cells of cysteine. However, the subsequent processes that are stimulated by cysteine starvation are unclear. Moffitt's researchers conducted a series of laboratory studies to find out which molecules are activated after cysteine deprivation and how this affects cells.
The researchers found that cancer cells can activate signaling pathways to protect themselves from cell death due to cysteine starvation. When the team stripped cysteine from non-small cell lung carcinoma cells, the cells began to undergo ferroptosis. However, the lack of cysteine also led to an unexpected accumulation of small molecules called α-glutamyl peptides, which protected the cells from ferroptosis. The researchers found that the peptides were synthesized due to the activity of the GCLC protein. Under normal conditions, GCLC is involved in the first stage of the synthesis of antioxidant glutathione from the amino acids cysteine and glutamate. However, this newly discovered GCLC activity occurred in the absence of cysteine and was important for limiting both glutamate accumulation and oxidant production.
"The transcription factor, NRF2, is known to play an important role in protecting against cellular oxidation and is often not regulated in lung cancer," said lead author Gina DeNicola, Ph. D., an assistant member of the Department of cancer physiology at Moffitt. "The ability of NRF2 to protect against ferroptosis is important for cancer, especially lung cancer, which typically has NRF2 activation via mutations in KEAP1 and NRF2."
Source: https://www.sciencedaily.com/releases/2021/01/210114130140.htm
