Nav: Home

Key player in cell metabolism identified

January 16, 2018

Barcelona, 16 january 2018.- Researchers from the Genomic Instability and Cancer Laboratory at Institute for Research in Biomedicine (IRB Barcelona) have identified a key role for EXD2 in protein production in the mitochondria, the cellular organelles responsible for the majority of energy generation.

"We have provided extensive evidence that EXD2 is a mitochondrial protein and that its main function is to facilitate the production of proteins in the mitochondria," explains Travis H. Stracker, head of the laboratory.

This work challenges the interpretation of previous studies that suggested that EXD2 performs a DNA repair function in the nucleus. "However, at this point we can't rule out other possible functions", declares Stracker.

Published in Nature Cell Biology, the study presents the results from a collaborative multidisciplinary approach, using state of the art proteomics, metabolomics, biochemistry, cell biology and the development of the fruit fly, Drosophila melanogaster, to pinpoint the function of EXD2.

Cleaning up the energy production process

Scientists identified the mitochondrial ribosome (or mitoribosome), the cellular machine required for protein production in the mitochondria, as a major interactor of EXD2. "EXD2 targets messenger RNA to keep the mitoribosome "clean" until it is mature and ready to generate proteins. In the absence of EXD2, cells are severely defective for mitochondrial protein production," explains Joana Silva, first author of the study and former PhD student of the Genomic Instability and Cancer Laboratory.

EXD2's role in the mitoribosome is critical for suppressing the generation of Reactive Oxygen Species (ROS), that can arise due to mitochondrial defects, and facilitating normal development in Drosophila. Flies lacking EXD2 showed increased ROS levels, delayed development and reduced fertility.

"The results highlight the complexity of mitochondrial protein production and demonstrate that many levels of regulation remain to be elucidated", says Stracker.

Potential target for metabolic disorders and cancer therapy

These studies may have implications for the understanding and treatment of metabolic disorders, such as diabetes, and cancer. In relation to the latter, in recent years, the importance of mitochondrial energy generation in tumors has been revisited and the inhibition of protein production has been proposed to be a therapeutic target by many groups.

As EXD2 is an enzyme and required for mitochondrial translation, it is possible that targeting it could have antitumoral effects, something that will be tested in future experiments.
-end-
This study was supported by the Ministry of Economy, Industry and Competiveness (MINECO), as well as the Finnish Cultural Society and the Fundação para a Ciência e a Tecnologia that funded the theses of the first two authors.

The work was performed in collaboration with several other labs that made important contributions, including Aidan Doherty in the University of Sussex, Brian Raught in the University of Toronto, Oscar Yanes in the Universitat Rovira i Virgili and Andreu Casali and Lluís Ribas de Pouplana in the IRB Barcelona.

Reference article:

Joana Silva, Suvi Aivio, Philip A. Knobel, Laura J. Bailey, Andreu Casali, Maria Vinaixa, Isabel Garcia-Cao, E?tienne Coyaud, Alexis A. Jourdain, Pablo Perez-Ferreros, Ana M. Rojas, Albert Antolin-Fontes, Sara Samino-Gené, Brian Raught, Acaimo Gonza?lez-Reyes, Lluis Ribas de Pouplana, Aidan J. Doherty, Oscar Yanes and Travis H. Stracker

EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome integrity and translation

Nature Cell Biology (2018) doi:10.1038/s41556-017-0016-9

Institute for Research in Biomedicine (IRB Barcelona)

Related Diabetes Articles:

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.
Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.
Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).
Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.
Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.
Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.
Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

How to Win Friends and Influence Baboons
Baboon troops. We all know they're hierarchical. There's the big brutish alpha male who rules with a hairy iron fist, and then there's everybody else. Which is what Meg Crofoot thought too, before she used GPS collars to track the movements of a troop of baboons for a whole month. What she and her team learned from this data gave them a whole new understanding of baboon troop dynamics, and, moment to moment, who really has the power.  This episode was reported and produced by Annie McEwen. Support Radiolab by becoming a member today at Radiolab.org/donate.