Effects of an indole chemical, mitochonic acid 5, in a mouse model of mitochondrial disease onset.

This study tested the effects of mitochonic acid 5 (MA-5) using a mouse model of mitochondrial disease onset (mito-mice∆), with disease resulting from the accumulation of pathogenic mitochondrial DNA harboring a large deletion (∆mtDNA). Administration of MA-5 to mito-mice∆ inhibited the progression of clinical symptoms, such as low body weight and lactic acidosis. In the kidneys, MA-5 protected against mitochondrial respiration defects and subsequent renal failure, even when ∆mtDNA accumulated to > 80%. In the heart, MA-5 also resolved the mitochondrial respiration defects. Our findings suggested that administration of MA-5 would be effective in delaying the progression of some mitochondrial diseases caused by mutant mtDNA and especially in mitochondrial-mediated renal failure.