News

News

Sunday
September, 25

May be significant for mitochondrial diseases, cancer, diabetes, age-related neurodegenerative disorders — ScienceDaily

[ad_1]

For the first time, researchers from Boston University School of Medicine (BUSM) have identified an ADP-ribosyltransferase enzyme that is active in the mitochondria (the organelle that generate most of the chemical energy needed to power biochemical reactions in cells) and characterized its activity. ADP-ribosyltransferases are enzymes that play a role in the modification of other proteins. The activity of this new mitochondrial enzyme, called NEURL4, is similar to that of PARP1, a nuclear enzyme well studied for its critical role in DNA damage repair and regulation of gene expression.

To characterize the enzymatic activity of NEURL4, the team led by first and co-corresponding author Maria Dafne Cardamone, PhD, former research assistant professor of biochemistry at BUSM, first performed in-vitro enzymatic assays. Then they generated a cell line in which NEURL4 was deleted using a gene editing system. From there they used mass spectrometry to compare the modifications on mitochondrial proteins in wild-type (“normal”) versus cells without NEURL4.

According to the researchers this approach led them to identify a number of mitochondrial proteins as targets of NEURL4, including mitochondrial LIG3, a protein involved in the repair of damaged mitochondrial DNA and confirmed that NEURL4 activity is required for the maintenance of mitochondrial DNA (mtDNA) integrity.

While this study does not have any direct implication for clinical treatments, the team says it represents an important step in understanding how cells maintain homeostasis and respond to oxidative stress. “While this will not directly improve people’s quality of life, we hope it will provide fertile grounds for new translational applications for the treatment of diseases with a mitochondrial component, such as cancer, diabetes, age-related neurodegenerative disorders and rare mitochondrial diseases” said co-corresponding author Valentina Perissi, PhD, associate professor of biochemistry and co-director of the Boston Nutrition Obesity Research Center at BUSM.

The researchers believe future studies investigating how NEURL4-mediated modifications of specific mitochondrial proteins affect mitochondrial functions could lead to the identification of novel regulatory strategies to target for therapeutic purposes. A better understanding of NEURL4 biology may also prove relevant for the treatment of male infertility. Mitochondrial DNA deletions are linked with reduced sperm mobility and infertility in both mice and humans and this research indicates that reduced NEURL4 expression in mice is associated with increased mtDNA deletions and markers of male infertility, such as reduced sperm count and increased sperm clumping.

Andrew Emili, PhD, and Julian Kwan, PhD, from the BU Center for Network Systems Biology (CNSB) collaborated on this research.

Funding for this study was provided by the National Institutes of Health (R01DK100422 and R01GM127625) to VP; Pilot and Feasibility Award to MDC from the Boston Nutrition and Obesity Center P30DK046200), and by the Grunebaum Cancer Foundation Fellowship to MDC.

Story Source:

Materials provided by Boston University School of Medicine. Note: Content may be edited for style and length.

[ad_2]

Source link

Find us on

Latest articles

- Advertisement - spot_imgspot_img

Related articles

Important 5 Things to Know before Starting Crossfit Training

Exercise is good for health. We all know about it and brands and the health industry agree...

Jason “The Athlete” MacDonald Approved CrossFit for MMA a...

Cross fit is a great exercise that helps in strengthening the body but also helps in building...

Here’s How and Why Boxing Conditioning Can Benefit CrossFit...

When you get into the ring, you never want to give up. It is all about how...

CrossFit World Champion Turned BJJ Blue Belt Explains Benefits...

The world of BJJ is a fascinating yet scary place. People are fascinated about the overall progress...

Lymphatic disorder may cause stillbirth or severe, chronic disease...

In a world first discovery, South Australian researchers have identified a genetic mutation responsible for a...

New fluorescent DNA label reveals nanoscopic cancer features —...

Researchers have developed a new fluorescent label that gives a clearer picture of how DNA architecture...