Unveiling the “Sayonara” Gene: Commonalities in Cell Death Across Species

Figure 1: The activation of the sayonara gene in fruit fly wings induces apoptosis, resulting in wing shrinkage. Credit: Adapted from Ref. 1 and licensed under CC BY 4.0. © 2023 Y. Ikegawa et al.

Contrary to traditional beliefs, fruit flies initiate programmed cell death, or apoptosis, using a cell-stress sensor similar to that of mammals.

Researchers from RIKEN have debunked the long-standing assumption that fruit flies lack a type of protein known as BH3-only, which triggers apoptosis. This discovery not only challenges previous beliefs but also highlights the similar mechanisms of apoptosis shared by fruit flies, humans, and nematodes.

The RIKEN team has identified a protein in fruit flies that, according to many textbooks, was believed not to exist. This protein detects cell stress and initiates a self-destruct sequence when the stress becomes excessive.

Programmed cell death or apoptosis is a self-elimination process undertaken by damaged cells within our bodies. This crucial process prevents cells from becoming cancerous, hence playing a vital role in maintaining our health.

The sophisticated molecular cascade driving apoptosis is initiated by a specific protein from a group known as BH3-only proteins. These proteins, responsible for stress detection in cells, are present in various animals, including mammals and nematodes.

However, for the past two decades, it was thought that fruit flies and potentially all insects lacked BH3-only proteins and relied on an alternate cell-death mechanism.

In an unexpected finding, Sa Kan Yoo and colleagues from the RIKEN Center for Biosystems Dynamics Research discovered a BH3-only protein in fruit flies. They named the encoding gene sayonara, after the Japanese word meaning ‘goodbye’.

Sa Kan Yoo (left) and Yuko Ikegawa. Credit: © 2023 RIKEN

When the research team activated the sayonara gene in the wings of fruit flies, they noticed the onset of apoptosis, leading to wing shrinkage (Fig. 1).

Yoo explains that the gene was always there, just overlooked. “We simply used the genetic sequence of a human BH3-only protein and compared it to the fruit fly genome—it’s a routine method for identifying genes in fruit flies that are similar to human ones,” he says.

Yoo suggests that the gene might not have been discovered in fruit flies 20 years ago due to the incomplete sequencing of their genome at that time. “The genome sequencing wasn’t comprehensive back then, so scientists possibly missed the gene and eventually gave up looking,” he explains.

The presumed absence of a BH3-only protein in fruit flies became a textbook fact, but Yoo found it intriguing. “I thought it would be interesting to examine it further,” he states, “and within a few hours, I identified something that greatly resembled a BH3-only protein.”

This discovery suggests that fruit flies, and likely other insects, share similarities with mammals and nematodes in their apoptosis mechanisms. “Fruit flies are not an anomaly or peculiar,” Yoo explains, “Rather, our findings show that they have a mechanism for regulating apoptosis that’s similar to that of humans and nematodes.”

The research team is now focusing on understanding what occurs after the activation of the BH3-only protein and investigating whether other insects possess BH3-only proteins.

Reference: “Evidence for existence of an apoptosis-inducing BH3-only protein, sayonara, in Drosophila” by Yuko Ikegawa, Christophe Combet, Mathieu Groussin, Vincent Navratil, Sabrina Safar-Remali, Takuya Shiota, Abdel Aouacheria and Sa Kan Yoo, 2 February 2023, The EMBO Journal.
DOI: 10.15252/embj.2021110454

Frequently Asked Questions (FAQs) about Apoptosis in Fruit Flies

More about Apoptosis in Fruit Flies

• Original Research in The EMBO Journal
• Apoptosis Basics by National Cancer Institute
• RIKEN Center for Biosystems Dynamics Research
• Introduction to Drosophila, the Fruit Fly Model Organism