Diseases of dysfunctional mitochondria, also known as mitochondrial diseases, have a prevalence of up to 1 in 2,000 people and predominantly affect children, though adult-onset disorders are also recognized. An international collaboration has discovered that mutations in the GTPBP3 gene cause defects in protein synthesis in mitochondria and are associated with a devastating disease.
Mitochondria are compartments present in every cell of the body except red blood cells and are responsible for generating almost all of the energy needed by the body to sustain life and to grow. In mitochondria, energy is produced by a large number of proteins, which are manufactured according to a blueprint, the cell’s DNA.
Patients affected by mitochondrial diseases have deficiency in energy production and suffer from heart and neurological disease.
Most of the proteins are encoded by DNA contained within the cell nucleus (nuclear DNA), however, the remaining portion is encoded within a small DNA molecule found inside mitochondria. This molecule is called mitochondrial DNA (mtDNA) or the mitochondrial genome. The mitochondrial DNA must be transcribed into RNA and the RNA translated into proteins. If the mitochondrial genome is not properly expressed, then mitochondrial proteins will not be properly made, and the cell will not be able to produce energy in a useful form.
A team has discovered that mutations in the GTPBP3 gene cause defects in protein synthesis in mitochondria and are associated with a devastating disease. Identification of mutations in nine unrelated families makes GTPBP3 an important new genetic factor responsible for human mitochondrial disease.
The collaborators analyzed patients’ DNA samples and found changes (mutations) in the GTPBP3 gene. They found that cells taken from the patients were unable to properly produce proteins in their mitochondria. To confirm that the mutations that they identified in the GTPBP3 gene are responsible for the disease they inactivated the gene in vitro in healthy cells. Inactivation of the gene in vitro caused these healthy cells to also be unable to properly synthetize proteins that are encoded in mtDNA.
The work identified a new gene, which widens the catalog of human genes associated with severe metabolic disorders. The findings allow for diagnosis of other patients affected with the disease and provides an opportunity for prenatal diagnosis. Further studies of processes in which GTPBP3 is involved will help towards the understanding of human diseases that are linked to mitochondrial DNA expression and to develop new therapies.
Citation: MRC Mitochondrial Biology Unit at Cambridge, 'Mutations in GTPBP3 Cause a Mitochondrial Translation Defect Associated with Hypertrophic Cardiomyopathy, Lactic Acidosis, and Encephalopathy' Volume 95, Issue 6, 4 December 2014, Pages 708–720 doi:10.1016/j.ajhg.2014.10.017
Source: Cambridge
