Nav: Home

An 'IRBIT'uary before cell death

December 20, 2016

Billions of cells in our bodies die every day in an important process called apoptosis. Now, researchers at the RIKEN Brain Science Institute have mapped out a sequence of events that are necessary for apoptosis to occur properly. Published in eLife, the study focuses on the protein IRBIT and how its action near mitochondria in our cells can set off a chain reaction that leads to programmed cell death.

Disruptions in proper apoptosis can lead to serious medical consequences. As team leader Katsuhiko Mikoshiba explains, "Excessive apoptosis in the brain is associated with several neurodegenerative diseases, while impaired apoptosis is related to some cancers and tumor formation."

Events that happen inside our cells are often controlled by interactions between proteins and modifications of proteins that change how they can interact with each other. Mikoshiba and his team have already shown that apoptosis in neurons can be initiated when certain proteins binds to IP3 receptors. In their new study, the team investigated IRBIT, another protein commonly found in the brain that can bind to the IP3 receptor.

In a series of studies, the researchers showed that the presence of IRBIT promoted normal apoptosis. "We were actually quite surprised," notes first author Benjamin Bonneau. "We initially expected that IRBIT would function to suppress cell death."

The reason for this prediction was that IRBIT has been primarily described as a protein that reduces cellular calcium levels, a phenomenon that can lead to cell death. Additionally, IRBIT is located in the same parts of the body--including the developing nervous system--as Bcl2l10, another protein that is known to reduce apoptosis and which also binds to the same region of the IP3 receptor as IRBIT. The key factor in this process is the flow of calcium ions between two organelles within a cell--the ER and mitochondria. When Bcl2l10 is attached to the IP3 receptor located in the ER membrane, it reduces the flow of calcium into the mitochondria, which prevents apoptosis.

In their new study, the team first showed that IRBIT and Bcl2l10 naturally attach to different places on the IP3 receptor, and that they attach to each other. This is why they initially thought that they work together to prevent apoptosis. However, further testing revealed an important event that always preceded apoptosis--IRBIT loses a phosphate group. Protein function is often altered through small additions or subtractions. The team showed that in this case, the loss of the phosphate group prevents IRBIT from staying attached to the IP3 receptor. Instead it moves away from the ER, and drags Bcl2l10 with it. When this happens, the team saw that without Bcl2l10, calcium flow into the mitochondria increased, which led to cell death.

Understanding IRBIT's role in facilitating apoptosis has implications for treating cancer that is associated with low levels of IRBIT expression. Bonneau notes that, "Because reduced IRBIT expression may contribute to tumor formation, the next step is to determine to what extent modulating IRBIT expression contributes to cancer formation, and if this is the case, what organs are the most sensitive.

Mikoshiba adds, "Neurodegenerative diseases such as Huntington's disease and Parkinson's disease are characterized by excessive apoptosis. Knowing IRBIT's involvement gives us a new target for investigation. As IRBIT is highly expressed in the brain, the chances are good that we will be able to find a connection, which could lead to new treatment possibilities."

Bonneau B, Ando H, Kawaai K, Hirose M, Takahashi-Iwanaga H, Mikoshiba K (2016). IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2110, and by promoting ER-mitochondria contact. eLife. doi: 10.7554/eLife19896


Related Mitochondria Articles:

Mitochondria-targeted antioxidant SkQ1 helps to treat diabetic wounds
Members of the Faculty of Biology and A.N. Belozersky Institute of Physico-Chemical Biology, a unit of the Lomonosov Moscow State University, have tested on a mouse model a mitochondria-targeted antioxidant, helping to treat diabetic wounds.
Mitochondria targeting anti-tumor compound
Researchers from Kumamoto University in Japan have found that the compound folic acid-conjugated methyl-BETA-cyclodextrin (FA-M-BETA-CyD) has significant antitumor effects on folate receptor-ALPHA-expressing (FR-ALPHA (+)) cancer cells.
Closing the gate to mitochondria
A team of researchers develops a new method that enables the identification of proteins imported into mitochondria.
Elucidated connection between renal failure and 'bad' mitochondria described
Biologists from the A.N. Belozersky Institute of Physico-Chemical Biology, a unit of the Lomonosov Moscow State University suggested the approach to prevent kidney injury after ischemia.
How exercise -- interval training in particular -- helps your mitochondria stave off old age
Researchers have long suspected that the benefits of exercise extend down to the cellular level, but know relatively little about which exercises help cells rebuild key organelles that deteriorate with aging.
Cell disposal faults could contribute to Parkinson's, study finds
A fault with the natural waste disposal system that helps to keep our brain cell 'batteries' healthy may contribute to neurodegenerative disease, a new study has found.
Sex cells evolved to pass on quality mitochondria
Mammals immortalize their genes through eggs and sperm to ensure future generations inherit good quality mitochondria to power the body's cells, according to new UCL research.
Newly identified pathway in mitochondria fuels tumor progression across cancer types
Scientists at The Wistar Institute have identified a novel protein pathway across several types of cancer that controls how tumor cells acquire the energy necessary for movement, invasion and metastasis.
Collapse of mitochondria-associated membrane in ALS
Mitochondria-associated membrane (MAM) is a contacting site of endoplasmic reticulum and mitochondria, and plays a key role in cellular homeostasis.
New research on the muscles of elite athletes: When quality is better than quantity
A Danish-Swedish research team working on a project led by University of Southern Denmark has discovered that muscle endurance is not only determined by the number of mitochondria, but also their structure.

Related Mitochondria Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...