Decreased Mitochondrial Membrane Potential Activates the Mitochondrial Unfolded Protein Response.

Mitochondria are ATP-producing organelles that also signal throughout the cell. Mitochondrial protein homeostasis is regulated through membrane potential-dependent protein import and quality control signaling. The mitochondrial unfolded protein response (UPR) is a specific program that responds to imbalances in nuclear and mitochondrial gene expression. Mounting evidence suggests that the electrochemical gradient that powers mitochondrial function, the mitochondrial membrane potential (Δψ), is a core regulator of the UPR. Here we tested this notion directly by pharmacologically dissipating Δψ and monitoring UPR activation. We found that chemical dissipation of Δψ using FCCP indeed activated UPR dose-dependently in assayed by the HSP-60::GFP reporter strain.