Scientists discover a new kind of cell death linked to copper

Plants and animals depend on copper for their survival. It helps blood clot, hormones mature, and cells process energy in humans. Scientists have figured out how copper kills cells.

The Broad Institute of MIT and Harvard have discovered a new form of cell death that is caused by copper. The team found that copper binding to specialized proteins causes them to form harmful clumps, and also interfered with the function of other essential proteins. Cells die when they go into a state of toxic stress.

The research identified which cells are vulnerable to copper-induced death by revealing key components of this process. The findings could help researchers better understand diseases in which copper is dysregulated, and could even inform the development of new cancer treatments. Science published the research.

Too little and cells can't survive, that's the double-edged sword of copper. Too much and cells die. It has been a mystery how excess copper is harmful, but we have finally figured it out, said Golub, who is also a member of the faculty of the Dana-Farber Cancer Institute and Harvard Medical School.

The carriers are made of copper.

The quest to understand copper-based toxicity began in the year 2019. They found that the copper carriers killed the cancer cells. One of the molecule, Elesclomol, had reached clinical trials as a potential cancer drug, but it failed to show efficacy in patients, as it was not known at the time how this molecule works. The researchers knew from their experiments that this kind of cell death is different from other forms of cell death. Tsvetkov wanted to know how copper kills cancer cells.

He said it became a basic cell biology question after he went down the rabbit hole.

The hypothesis that the toxicity of the copper carriers stems from copper itself was systematically tested by the researchers. They showed that the process of cell death was dependent on the availability of copper. The researchers found that cuprotosis is different from other forms of cell death. The cells that were treated with copper ionophores still died when the researchers blocked known pathways of cell death.

The team talked about how copper carriers kill cells. They found that cells that relied on mitochondria to produce energy were more sensitive to copper ionophores than cells that used sugar. The team used multiple screens to identify genes that facilitate death.

The genes include FDX1, which is involved in a chemical modification of a small number of genes in the mitochondria that is essential for metabolism. The researchers found that copper delivered to the mitochondria by the ionophores causes them to form long chains and clumps that lead to cell death. They discovered that copper interfered with iron-sulfur clusters. The stress caused cells to die, as the downregulation of the enzymes pushed them into a toxic state.

There are hidden signs.

The scientists suggest that their study could shed light on a variety of biological processes, including those in organisms that produce copper ionophores with antimicrobial properties, and in people with genetic disorders.

One of the copper ionophores, Elesclomol, failed its clinical trial as a cancer therapeutic, but later analysis showed that it helped patients whose tumors rely on mitochondria for energy production. Elesclomol could potentially be used to treat a range of cancers that are vulnerable to the process, such as those expressing FDX1, after the team found markers of copper-induced cell death.

Tsvetkov is eager to learn more about new organisms or diseases that might be related to copper-induced cell death. He hopes the findings will inspire new research.

He said that a new mechanism and some elements that are essential for this process have been revealed.

More information: Peter Tsvetkov et al, Copper induces cell death by targeting lipoylated TCA cycle proteins, Science (2022). DOI: 10.1126/science.abf0529 Journal information: Science Citation: Scientists discover a new kind of cell death linked to copper (2022, March 18) retrieved 18 March 2022 from https://phys.org/news/2022-03-scientists-kind-cell-death-linked.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.