Chapter 15, Problem 26P

Many clinically relevant mitochondrial diseases are caused by mutations in mitochondrial genes affecting tRNAs. For example, one form of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is caused by a point mutation in the gene encoding the mitochondrial tRNA whose anticodon recognizes the codons 5′ UUA and 5′ UUG. The mutation makes the aminoacylation of this tRNA inefficient.

a.	The rate of synthesis of most mitochondrial proteins is either unaffected or slightly decreased in MELAS cells, but one mitochondrial protein called NAD6 is synthesized at only 10% of the normal rate. How is it possible that the translation of this single mitochondrial protein might be affected specifically?
b.	Why might the decreased translation of this one protein be responsible for the pathological condition?
c.	Researchers are currently investigating ways to treat the symptoms of MELAS patients. One strategy involves a change to a nuclear gene. What nuclear gene might the investigators be targeting? (Assume that you can make any desired change to nuclear genes; we will describe methods to alter genomes in Chapter 18.)