Mitochondrial tRNA mutant causes metabolic defects

Mitochondria are cellular organelles that use oxidative phosphorylation to convert the energy of reduced dietary carbon into ATP, which provides energy for practically all processes. Human mitochondria possess a mostly vestigial 16 kb genome, which encodes ribosomal and 22 transfer RNAs along with 13 proteins. There are more mitochondria in cells with high energy needs such as heart muscle cells, where mitochondria and myofibrils make up 85% of cell volume. Cardiovascular disease is associated with high blood pressure and high serum cholesterol. These investigators analyzed the genetics of a syndrome that includes hypertension (blood pressure >140/90 mm Hg), hypercholesterolemia (serum cholesterol >200 mg/dl), and hypomagnesemia (serum magnesium below 1.8 mg/dl) in 4 generations of a large family. A genome-wide linkage
analysis yielded no candidates. They found that the 32 family members of both sexes with hypomagnesemia all descended from one female, suggesting a mitochondrial defect. Upon sequencing and single-strand conformational polymorphism analysis, they found 14 variants, 13 of which were previously described, and one new variant at nucleotide 4291 of the mitochondrial genome, within an isoleucine tRNA. This tRNA mutation is found only on this maternal lineage, not among the thousands of previously sequenced mitochondrial genomes.
Wilson et al. Science 306: 1190, November 2004