Mitochondrial disease therapies directed at intra-mitochondrial pathology are largely ineffective. Recognizing that RC dysfunction invokes pronounced extra-mitochondrial transcriptional adaptations, particularly involving dysregulated translation, we sought to determine the therapeutic efficacy and mechanisms by transcriptome profiling of pharmacologically inhibiting the mTORC1 signaling pathway with rapamycin or probucol, or by partially inhibting cytosolic translation with cycloheximide, in the well-established C. elegans gas-1(fc21) animal model of primary mitochondrial respiratory chain dysfunction.