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^mt) 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_m), is a core regulator of the UPR^mt. Here we tested this notion directly by pharmacologically dissipating Δψ_m and monitoring UPR^mt activation. We found that chemical dissipation of Δψ_m using FCCP indeed activated UPR^mt dose-dependently in C. elegans assayed by the HSP-60::GFP reporter strain.