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)... ... October 13, 2017 , ... Global Healthcare Management’s 4th Annual Kids Fun Run ... This free event, sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed ... geared towards children of all ages; it is a non-competitive, non-timed event, which is ...
(Date:10/13/2017)... ... October 13, 2017 , ... “The Journey: From the Mountains ... possible to save lost souls in the Philippines. “The Journey: From the Mountains to ... dedicated teacher of the Bible. She has taught all ages and currently teaches a ...
(Date:10/12/2017)... ... 12, 2017 , ... Planet Fitness, one of the largest and fastest growing ... open a flagship location in Covington, LA at 401 N. U.S. Highway 190, in ... to Office Depot in the Holiday Square shopping center. Its location allows it to ...
(Date:10/12/2017)... ... October 12, 2017 , ... Asante, a nationally recognized ... have expanded their existing home health joint venture through an agreement, effective October ... a joint venture home health company with Asante, delivering clinically integrated care, for ...
(Date:10/12/2017)... ... October 12, 2017 , ... Leading pediatric oncology experts at Children’s ... the 49th Congress of the International Society of Paediatric Oncology (SIOP) Oct. ... Center for Cancer and Blood Disorders at Children’s National, and Stephen P. Hunger, ...
Breaking Medicine News(10 mins):
(Date:10/2/2017)... 2017 The Rebound mobile app is poised to ... the tide of prescription drug addiction. The app empowers users ... and stepping down their dosage in a safe, controlled manner ... 2017; the first 100,000 people to sign up will enjoy ... ...
(Date:9/27/2017)... Sept. 27, 2017  Commended for their devotion to personalized ... Ranked as number one in the South Florida Business Journal,s ... Inc. 5000 yearly list, the national specialty pharmacy has found ... Bardisa will soon be honored by SFBJ as the ... Set to receive his award in October, Bardisa ...
(Date:9/25/2017)... , Sept. 25, 2017  EpiVax, Inc., ... vaccine design, and immune-engineering today announced the launch ... the development of personalized therapeutic cancer vaccines. EpiVax ... provided exclusive access to enabling technologies to the ... MBA will lead EpiVax Oncology as Chief Executive ...
Breaking Medicine Technology: