Mitochondrial disorders are a group of diseases that take many different forms and vary greatly from person to chameleon .
mitochondria are present in specific organelles of cells which produce most of the chemical energy that powers cellular operations. mitochondrial dysfunction has been associated with a wide variety of diseases, including autism, Alzheimer's disease, schizophrenia, dementia, Parkinson's disease, epilepsy, stroke, cancer, fatigue syndrome and chronic cardiovascular diseases.
There are a number of different factors that can cause mitochondria to misbehave. However, mutations in mitochondrial DNA (mtDNA) are known to play a disproportionate role. Now a team of researchers from Vanderbilt University found that the mutant mtDNA can cause diseases by acting "selfishly." - In a way that is beneficial them while harming their host
The Vanderbilt researchers identified the specific molecular mechanisms selfish use of mutant mtDNA to bypass molecular control mechanisms that cells have developed to regulate mitochondrial activity. Detailed understanding of these molecular pathways could help researchers to develop effective treatments for mitochondrial diseases.
Prevalence mitochondrial disorders
"About a newborn on 0 inherits a potentially pathological mitochondrial disease that occurs in about one adult in 5000," said the assistant professor of science biological Maulik Patel, who led the Vanderbilt researchers. Their work is described in the "dynamic homeostatic responses regulate selfish mitochondrial genome of C. elegans," published in the July 12 issue of the journal Cell Metabolism.
team members who contributed to the study were Vanderbilt PhD and Bryan Gitschlag Cait Kirby and associate professor of molecular physiology and biophysics David Samuels, Senior Research Specialist and Gangula Rama and Simon Mallal Major EB Shulman, professor of infectious diseases and inflammation at Vanderbilt school of Medicine.
"Once we know the mechanisms that mutant mitochondria use to escape the cell regulation, then we can develop drugs that target these pathways and prevent the spread of mutations," said Patel.
mitochondria are a unique feature in eukaryotic cells, the cell types found in plants and animals. The generally accepted theory is that mitochondria were originally independent bacteria that have developed an ability to use highly toxic oxygen molecules as a source of powerful energy: a capacity that prokaryotic cells lacking. So some prokaryotes have found ways to convert the mitochondria in a "endosymbiont," an organism that lives in the body of another organism. According to a popular theory, this symbiosis was so successful that it has provided eukaryotes with the added energy they need to start forming multicellular organisms.
Powerhouse of the cell
Although self contained mitochondria are generally known by their role as "the power of the cell," they are also involved in a number of other cellular activities, including cell cycle regulation and cell growth
one of the things that are. single mitochondria is that they have managed to maintain their own DNA through the process of endosymbiosis. the mitochondrial genome is extremely small compared to the massive human genome and consists of a closed ring of 37 genes inherited only from the mother.
the number of copies of mitochondrial DNA in human cells differs widely depending on the type of cell. for example, human blood cells do not carry at all as human liver cells can harbor more thousands of copies each.
in a normal cell, all copies of mtDNA is the same. However, cells contain molecular mechanisms dismantle and destroy components of unnecessary or malfunctioning cells, including the mitochondria. Consequently, these organelles may be reproduced and destroyed at a very high pace. In the resulting mixture, mutant mtDNA can occur. If they reach high levels they become pathogenic.
unusual properties of mitochondrial diseases
mitochondrial disorders have unusual properties. "Unlike bacterial infections that tend to be all or nothing, mitochondrial infections can range from zero to 100 percent," said Patel. "This makes multi-symptomatic mitochondrial disorders, with many individual differences. A person with a mutant load of 50 percent could be symptom free while another person with 80 percent may have severe symptoms. "In addition, mitochondrial diseases are passed from mother to child, except for developmental disorders, tend to develop later in life.
Patel and his colleagues studied the nature of mitochondrial diseases in the transparent roundworm Caenorhabditis elegans (C. elegans for short), a model animal widely used to explore the basic processes in the development and behavior of multicellular organisms, including humans.
How mutant mtDNA escape of a cell mechanism control regulation
researchers found that cells activate two specific responses to treat mitochondrial dysfunction resulting due to the presence of mutant mtDNA. Paradoxically, however, these same responses allow inadvertently mutant mtDNA from spreading further and proliferate. "In this perspective, the mutant mtDNA can be considered selfish entities that operate regulatory control mechanisms of cells for their own evolutionary interests," said Patel.
mitochondrial genome copy number
the cells have a way to count the number of normal mitochondrial genomes they have. This allows them to make more mitochondrial genomes when they need more energy. the researchers found evidence supporting the prediction co-author Samuels some mutant mitochondrial genomes are invisible to the counting of the machinery of the cell. as a result, cells make more copies of the mutant genomes in a futile quest to achieve optimum energy levels. the end result is harmful over-production of mutant copies.
mitochondrial unfolded protein response
the cells continuously monitor the health status of their mitochondria. When they detect mitochondrial dysfunction, cells try to repair the problem with a procedure called the response of the mitochondrial protein unfolded. In addition to relieving the dysfunction in the mitochondria, the procedure protects against destruction by the cell disassembly mechanisms. Researchers have found evidence that some mutant mitochondria can activate this response, which causes the cell to tolerate their presence and allows the mutant mtDNA to proliferate.
"These are the two cases where the mutant mitochondrial genomes operate cellular defenses for their own interests" selfish "," said Patel.
