Navigation Links
How mitochondrial DNA defects cause inherited deafness
Date:2/17/2012

New Haven, Conn. Yale scientists have discovered the molecular pathway by which maternally inherited deafness appears to occur: Mitochondrial DNA mutations trigger a signaling cascade, resulting in programmed cell death. The study is in the Feb. 17 issue of Cell.

Mitochondria are cellular structures that function as "cellular power plants" because they generate most of the cell's supply of energy. They contain DNA inherited from one's mother. Mitochondria determine whether a cell lives or dies via the process of programmed cell death, or apoptosis.

The Yale scientists focused on a specific mitochondrial DNA mutation that causes maternally inherited deafness. The mutation occurs in a gene that codes for RNA in mitochondrial ribosomes, which generate proteins required for cellular respiration. The team found that cell lines containing this mutation are prone to cell death not directly due to the mutation, but rather because it enhanced a normal chemical modification of the RNA called methylation, which regulates ribosome assembly.

"Our lab had previously discovered that overexpression of the enzyme responsible for this methylation could cause cell death, even in cells without the deafness mutation," said corresponding author Gerald S. Shadel, professor of pathology and genetics at Yale School of Medicine. "But when the researchers overexpressed the enzyme in mice to mimic the effects of the mutation," he said, "we were astonished to discover that the animals progressively lost their hearing, reflecting how such disease would develop due to a known pathogenic human mitochondrial DNA mutation. This new mouse model will be instrumental in understanding genetic and environmental factors known to impact mitochondrial disease pathology."

The researchers found that reactive oxygen molecules produced by diseased mitochondria are what trigger events leading to a cell death-inducing gene expression program. By genetically depleting the protein ultimately responsible for activating this programmed cell death response, they were able to restore normal hearing to the mice.

The study not only sheds light on inherited deafness in humans, but possibly also age-related hearing loss and other human diseases. First author Nuno Raimundo, a postdoctoral associate in pathology, said, "Mitochondrial diseases are complicated because different tissues are affected in often unpredictable ways. Defining the molecular mechanism underlying death of only a specific subset of cells in the inner ear is a major step toward unraveling this complexity."


'/>"/>
Contact: Helen Dodson
helen.dodson@yale.edu
203-436-3984
Yale University
Source:Eurekalert

Related medicine news :

1. New mitochondrial control mechanism discovered
2. Animal results may pave way to treating rare mitochondrial diseases in children
3. Exposure to BPA may cause permanent fertility defects, Yale researchers find
4. Low blood oxygen may lead to heart defects in children with sickle cell disease
5. Many Non-U.S. Firms Affected by U.S. FDA Import Alert 80-04 for Medical Glove Manufacturing Defects, According to FDAImports.com, LLC
6. Psychotropic medications can cause birth defects
7. Experts Believe Many Birth Defects Are Preventable
8. Study implicates new epigenetic player in mental retardation and facial birth defects
9. Pediatric urologist performs innovative procedure for girls with rare vaginal defects
10. Growth defects in cystic fibrosis may start before birth
11. Doubled risk of anxiety for 18 month-old children with congenital heart defects
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... VA (PRWEB) , ... October 13, 2017 , ... ... of DevOps and Agile Software Development, has been awarded a contract by the ... Blanket Purchase Agreement (BPA) aims to accelerate the enterprise use of Agile methodologies ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent and San Francisco dentists, ... cutting-edge Oventus O2Vent technology. As many as 18 million Americans are estimated to ... breathing. Oral appliances can offer significant relief to about 75 percent of people ...
(Date:10/12/2017)... ... October 12, 2017 , ... The American College of Medical ... Friedman, PhD, FACMI, during the Opening Session of AMIA’s Annual Symposium in Washington, D.C. ... honor of Morris F. Collen, a pioneer in the field of medical informatics, this ...
(Date:10/12/2017)... ... ... HMP , a leader in healthcare events and education, today announced that ... for ‘Best B-to-B Healthcare Website.’ Winners were announced during the Eddie & Ozzie Awards ... recognizes editorial and design excellence across a range of sectors. This year’s program included ...
(Date:10/12/2017)... ... , ... Health Literacy Innovations (HLI), creator of the Health ... Cancer Patient Education Network (CPEN), an independent professional organization that shares best practices ... , As CPEN’s strategic partner, HLI will help support CPEN members by ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... Oct. 12, 2017 AVACEN Medical , Inc. ... with their  2017 New Product Innovation Award for Its ... primary and secondary medical device market research by Frost & ... first-to-market OTC, drug-free pain relief product, the AVACEN 100, offers ... treating fibromyalgia widespread pain. ...
(Date:10/11/2017)... Oct. 11, 2017  True Health, a leader ... its effort during National Breast Cancer Awareness month ... risks. Research ... calculated that more than 10 million American women ... in BRCA1 or BRCA2 and have not had testing. ...
(Date:10/5/2017)... 2017  In response to the nationwide opioid ... Surgeons (AAOMS) released prescribing recommendations that urge ibuprofen ... as a first-line therapy to manage a patient,s ... Recognizing the value and importance of ... Prescribing: Acute and Postoperative Pain Management" stresses that ...
Breaking Medicine Technology: