Extended Data Figure 8.

a, Diagram of the mevalonate pathway for the biosynthesis of cholesterol, ubiquinone and heme A, and protein N-glycosylation and prenylation. b, hsp-6p::gfp animals treated with antimycin after pre-treatment with increasing concentration of simvastatin. c, hsp-6p::gfp animals with mock, 80ug/ml simvastatin or 80ug/ml mevastatin treatment. d, hsp-6p::gfp animals raised on control RNAi, hmgs-1 RNAi, or hmgs-1 RNAi with the addition of geranylgeranyl pyrophoshate. The animals were then treated with antimycin to induce mitochondrial damage. Statin toxicity has been proposed to be caused by the inhibition of Rab prenylation²⁴. Geranylgeranyl pyrophosphate (GGPP), a precursor of protein prenylation rescued the statin side effect in cell culture²⁴. GGPP also partially rescued the deficiency of mitochondrial surveillance and activated hsp-6p::gfp in antimycin-treated hmgs-1(RNAi) animals.