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Mitochondrial Mutations Contribute to Autoimmune Disease?

Mitochondria, the cell's power plants, contain their own DNA. This is a legacy of their origin as symbiotic bacteria, but it makes them vulnerable to damage. Mitochondrial DNA is not as well protected and maintained in comparison to nuclear DNA, and it sits right next to an energetic biochemical process that generates plenty of potentially harmful reactive oxygen species. More serious mutational damage such as deletions are thought to contribute to aging by creating mitochondria that lack the proteins needed for proper function. Here, however, researchers speculate that other types of mutation that alter the produced proteins rather than block their production can contribute to the development of autoimmune disease:

Autoimmune disease is a critical health concern, whose etiology remains enigmatic. We hypothesized that immune responses to somatically mutated self proteins could have a role in the development of autoimmune disease. IFN-γ secretion by T cells stimulated with mitochondrial peptides encoded by published mitochondrial DNA was monitored to test the hypothesis. Human peripheral blood mononuclear cells (PBMCs) of healthy controls and autoimmune patients were assessed for their responses to the self peptides and mutated-self peptides differing from self by one amino acid.

None of the self peptides but some of the mutated-self peptides elicited an immune response in healthy controls. In some autoimmune patients, PBMCs responded not only to some of the mutated-self peptides, but also to some of the self peptides, suggesting that there is a breach of self-tolerance in these patients. Although PBMCs from healthy controls failed to respond to self peptides when stimulated with self, the mutated-self peptide could elicit a response to the self peptide upon re-stimulation in vitro, suggesting that priming with mutated-self peptides elicits a cross-reactive response with self. The data raise the possibility that DNA somatic mutations are one of the events that trigger and/or sustain T cell responses in autoimmune diseases.

Link: http://dx.doi.org/10.1016/j.humimm.2014.06.012

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