A woman who suffers from frequent and severe migraine headaches has had five children, all of whom have experienced, beginning between the ages of 8 and 12, stroke-like episodes compounded with exercise intolerance and lactic acidosis. The father of the children does not suffer from migraines, nor is he exercise intolerant. A target of a mutation that can explain these findings is most likely which one of the following?
A summary of the electron transfer chain and oxidative phosphorylation inhibitors is presented in Table below.The children have all inherited a mixture of normal and defective mitochondria (mitochondria with mutations in their genome) from their mother and are experiencing MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). The degree to which the children express these symptoms is dependent on the segregation of normal and mutant mitochondria during embryogenesis (heteroplasmy). Eighty percent of MELAS mutations are caused by alteration in the mitochondrial tRNAleu, leading to improper translation of proteins from the mitochondrial genome. One key to mitochondrial inheritance is that all children from an affected mother will be variably affected (variable expressivity, even though the disorder is 100% penetrant), whereas no children of an affected father would exhibit symptoms of the disease.Inhibitors of Oxidative PhosphorylationInhibitorSite of InhibitionRotenone, amytalTransfer of electrons from complex I to coenzyme Q.Antimycin CTransfer of electrons from complex III to cytochrome c.Carbon monoxideTransfer of electrons from complex IV to oxygenCyanideTransfer of electrons through complex IV to oxygenAtractylosideInhibits the ANTOligomycinInhibits proton flow through the F0 component of the ATP synthaseDinitrophenolAn uncoupler; facilitates proton transfer across the inner mitochondrial membraneValinomycinA potassium ionophore; facilitates potassium ion transfer across the inner mitochondrial membrane
Mitochondrial tRNA
Cytoplasmic tRNA
Cytochrome c
Pyruvate dehydrogenase
Miscellaneous (Bio-Chemistry)