Science & Technology

A new type of cell death found in the intestine of flies

Like the skin, the cells that make up the intestine are constantly dying and being replaced by new cells. This process, called turnover, helps maintain the balance between tissue growth and tissue regeneration, or homeostasis. The traditional theory of intestinal turnover is that aged or damaged cells die through a process called apoptosis. Apoptosis, also known as “programmed cell death,” is one of three currently recognized types of cell death. New studies question this assumption and provide evidence of a second type of programmed cell death that may be unique to the gut.

As is often the case, this discovery happened by accident. Researchers were studying a fruit fly version of ANCE, an enzyme that helps lower blood pressure. They found that the expression of Ance in the intestine of flies was patchy and that the cells containing it had strange characteristics. “We found that Ance labels some strange cells in the fruit fly’s gut,” says Yoo. “But it took us a long time to realize that these strange cells were actually dead.” They said that the strange cells were dark, nuclear envelope, mitochondria, cytoskeleton, and sometimes. We have discovered that cells lack the DNA and even other cellular items they need to stay alive.

Enterocytes at various stages of elebosis.
During elebosis, fluorescent proteins such as GFP and RFP are lost and the cells become “black”. At the onset of elebosis, cells lose cytoplasmic GFP (lower left cell). Elevotic cells then lose nuclear GFP (central cell) and nuclear RFP (upper center cell).

This process is very gradual, and unlike the more abrupt and explosive cell death seen in apoptosis, they realized that it could be something new. It was theorized that new types of cell death are associated with intestinal turnover, as Ance-positive cells are often near where new cells are born in the intestine. They tentatively named it Process Erebus, based on the Greek word “Erebus” meaning “darkness” because the dying cells looked so dark under the microscope.

To prove that elebosis is a new type of cell death, researchers have conducted several tests. First, experimental arrest of apoptosis did not interfere with intestinal homeostasis. This meant that cell turnover in the intestine, including cell death, could proceed without apoptosis. Second, dying cells showed neither apoptosis nor two other types of known cell death molecular markers. Late elevosis cells showed a common marker of cell death associated with degraded DNA.

A detailed examination of the cells undergoing elebosis revealed that they were located near a cluster of intestinal stem cells. This is good evidence that the electrified cells were replaced by newly differentiated enterocytes during the turnover. Ironically, knocking down or overexpressing Ance did not affect turnover or elevosis, so the enzyme that led to this discovery does not appear to be directly involved in the process. Therefore, the next step is to elucidate the detailed molecular events that enable elebosis and cell turnover in the fly’s gut.

“I feel that our results can be an original discovery. Personally, this is the most groundbreaking study I have ever done.” “I am very interested in the presence of elevosis not only in Drosophila but also in the human intestine,” he said.

A new type of cell death found in the intestine of flies A new type of cell death found in the intestine of flies

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