Genome wide transcriptional change by oligomycin or manipulation of mitochondrial membrane potential

Oligomycin, an inhibitor of ATP synthase (Complex V), increases mitochondrial membrane potential (ΔΨm) and induces ISR. Since direct manipulation of mitochondrial membrane potential using the genetic reagent that we developed (UCP1) rescued the effect of oligomycin on ISR, we performed RNAseq to investigate the effect of direct manipulation of ΔΨm by UCP1 on transcription. RNAseq analysis showed that direct manipulation of ΔΨm does not induce a major transcriptional program. However, oligomycin treatment caused a significant change in the expression of many genes, and the activation of UCP1 under oligomycin treatment rescued most of the transcriptional changes.