Discovery may lead to mitochndria syndrome treatment

September 22, 2011 By Krishna Ramanujan, Cornell University
This figure shows the protein encoded by the newly identified human gene, DHFRL1, localizing to mitochondria. The blue stain illuminates the cell nucleus, and the green fluoresce shows the co-localization of DHFRL1 and a mitochondrial marker.

Mitochondrial depletion syndrome accounts for about 11 percent of the cases of children born with common myopathies and a more mild form of the syndrome affecting adults. A new finding by Cornell researchers may lead to a nutrition-based treatment with B vitamins.

The syndrome can cause , muscle weakness and myopathy (a muscular disease in which lose function) and can be fatal in children; it can generate exercise intolerance, fatigue, anemia and neuropathy (disorders due to damaged nerves of the parts of the nervous system outside the brain and spinal cord) in adults.

Mitochondria are known for supplying cells with energy, along with many ranging from cell growth and signaling to cell death. Though the syndrome is commonly associated with genetic mutations, the details have been largely unknown.

Now, Cornell researchers have identified a new human gene, called DHFRL1, and an associated pathway that is required for faithful replication and stability of , according to the study, which was published Aug. 26 in the .

"We have found a new pathway, which when disrupted, may explain mitochondrial depletion syndrome in a subset of adults and children," said Patrick Stover, professor and director in the Division of Nutritional Sciences and the senior author of the study. Donald Anderson, a former graduate student in Stover's lab and now a postdoctoral associate at the University of Texas Southwestern, is the paper's lead author.

The study describes a pathway in which the DHFRL1 gene and two other genes, SHMT2 and TYMS, express proteins that lead to the synthesis of dTMP, a nucleotide that serves as a building block of mitochondrial DNA. The pathway is needed for faithful replication of mitochondrial DNA and leads to genomic stability.

When Stover and colleagues knocked out the DHFRL1 gene, the pathway was disrupted, leading to mitochondrial DNA instability, which is the hallmark of the depletion syndrome.

The vitamin folate (naturally occurring B-9, also known as folic acid, in its synthetic form) is essential to the pathway's proper functioning.

In the United States, food is fortified with folic acid, but for individuals who have that lead to folate deficiency or an inability to use folate properly, vitamin B-9 supplementation could improve their health, Stover said.

"Pathologies related to B vitamin folate are common in the United States and worldwide, and this study sheds new light on the role of folate and in the body and has implications for treating mitochondrial depletion syndrome," said Stover.

Related Stories

Recommended for you

Could vitamin B3 treat acute kidney injury?

August 20, 2018
Acute kidney injury, an often fatal condition without a specific treatment, affects up to 10 percent of all hospitalized adults in the United States and 30-40 percent in low-income countries. The condition causes a build-up ...

New assay to detect genetic abnormalities in sarcomas outperforms conventional techniques

August 20, 2018
Sarcomas are rare tumors that are often misdiagnosed. Specific recurrent chromosomal rearrangements, known as translocations, can serve as essential diagnostic markers and are found in about 20 percent of sarcomas. Identification ...

Team develops new way to grow blood vessels

August 17, 2018
Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed ...

New imaging technique can spot tuberculosis infection in an hour

August 16, 2018
Guided by glowing bacteria, researchers have devised an imaging technique that can diagnose live tuberculosis in an hour and help monitor the efficacy of treatments. That's particularly critical because many TB strains have ...

Obesity, infertility and oxidative stress in mouse egg cells

August 16, 2018
Excessive body fat is associated with negative effects on female fertility and pregnancy. In mice, maternal obesity impairs proper development of egg precursor cells called oocytes. In a recent paper published in Molecular ...

Research shows it's possible to reverse damage caused by aging cells

August 15, 2018
What's the secret to aging well? University of Minnesota Medical School researchers have answered it- on a cellular level.

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.