New gene expression analysis paves way for improved disease diagnosis and treatment

November 15, 2017, Max Planck Society

A comprehensive new analysis from the Max Planck Institute for Biology of Ageing, Germany, and Karolinska Institutet, Sweden, provides insight on how the dysfunction of an important biological process causes disease.

The study in mice, published today in eLife, could open new avenues for research into the deficiency of a system called oxidative phosphorylation (OXPHOS) and provide a valuable reference for future diagnosis and treatment.

OXPHOS is a metabolic process whereby cells release energy from the food we eat by using enzymes to harvest it and convert it into a molecule called adenosine triphosphate, the cell's fuel. It is produced by structures called mitochondria. Given this central role, is a major contributor to human disease and is also involved in the aging process.

"The molecular consequences of OXPHOS dysfunction are hard to predict," says lead author Inge Kühl. "Recent advances in high-throughput technologies in proteomics, metabolomics and sequencing have increased our knowledge of . However, the events that accompany OXPHOS dysfunction and contribute to are still poorly understood and the treatment options are limited."

To help fill this knowledge gap, Larsson and his team analysed five strains of mice that were deficient in essential factors needed for mitochondrial DNA gene expression in the heart, subsequently leading to OXPHOS dysfunction.

Using an integrated sequencing and mass spectrometry approach, the scientists compared the animals' mitochondrial and cellular proteomes. The team then listed the various gene expression changes at the RNA and protein levels in the mice, caused by OXPHOS dysfunction. Surprisingly, they identified a novel response to OXPHOS dysfunction across all the animals, whereby enzymes in the mitochondria that are necessary for the production of ubiquinone (Q) were severely reduced.

"Q is an essential electron shuttle in the mitochondrial respiratory chain," explains senior author Nils-Göran Larsson, director of the Max Planck Institute for Biology of Ageing and the Institute's Mitochondrial Biology department. "Its deficiency, caused by impaired mitochondrial DNA gene expression in the mouse heart, could potentially be a target for future therapeutics."

"Altogether, our comparative analyses provide a high-quality resource of altered gene expression patterns under OXPHOS deficiency," adds co-author Maria Miranda, PhD student at the Max Planck Institute for Biology of Ageing. "Our datasets can be mined for future studies in this area and will hopefully contribute towards improved patient diagnosis and research on future treatment strategies."

Explore further: Genetic signature linked to cancer prognosis identified

More information: Inge Kühl et al, Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals, eLife (2017). DOI: 10.7554/eLife.30952

Related Stories

Genetic signature linked to cancer prognosis identified

October 10, 2016
Researchers from the Medical Research Council (MRC) Cancer Unit at the University of Cambridge have identified a genetic signature related to metabolism associated with poor patient prognosis. The results of the analysis ...

Study reveals possible treatment for diseases caused by Mitofusin 2 deficiency

February 16, 2015
Researchers have discovered a novel role for Mitofusin 2, and the findings may point to a new treatment for patients with diseases caused by loss of the mitochondrial protein. The study appears in The Journal of Cell Biology ...

Higher number of mitochondrial DNA-molecules can compensate for negative effects of mutations

August 4, 2017
Male infertility can be caused by mutations in the DNA of mitochondria, the powerhouses of cells. By increasing the total DNA amount in mitochondria, scientists from the Max Planck Institute for Biology of Ageing in Cologne ...

High-intensity training delivers results for older men-but not for older women

September 11, 2015
High-intensity training (HIT) is often recommended as a way to improve cardiovascular fitness in men and women. HIT exercise can have a positive effect on a person's maximum oxygen consumption (VO2max) and mitochondrial oxidative ...

Researchers sniff out potential Leigh syndrome treatment

July 18, 2016
A mouse with dysfunctional mitochondria may hold the key to treating Leigh syndrome in humans.

Recommended for you

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Researchers give new insight to muscular dystrophy patients

December 13, 2018
New research by University of Minnesota scientists has revealed the three-dimensional structure of the DUX4 protein, which is responsible for the disease, facioscapulohumeral muscular dystrophy (FSHD). Unlike the majority ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.