How mitochondrial DNA defects cause inherited deafness
How mitochondrial DNA defect causes inherited hearing loss.
(Medical Xpress) -- 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 ones 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.
Provided by Yale University
- Mitochondrial DNA mutations can cause degenerative heart and muscle disease Feb 14, 2008 | not rated yet | 0
- Immune cells kill foes by disrupting mitochondria 2 ways May 15, 2008 | not rated yet | 0
- Genetic defect suggests high blood pressure may come from mom Mar 31, 2011 | not rated yet | 0
- New mitochondrial control mechanism discovered May 04, 2011 | not rated yet | 0
- Researchers uncover new role for mitochondria during RNA processing Mar 16, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
4 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
10 hours ago | 5 / 5 (3) | 0 |
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
7 hours ago | 5 / 5 (1) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
4 hours ago | not rated yet | 0
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
7 hours ago | 5 / 5 (2) | 0 |
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
5 hours ago | not rated yet | 0