Figure 1. FCCP dose-dependently activates the mitochondrial unfolded protein response (UPRmt): A) Schematic depicting transcriptional control of the UPRmt. The UPRmt transcription factor (ATFS-1 in C. elegans) is imported to mitochondria according to the mitochondrial membrane potential (Δψm) and degraded. Δψm is denoted by "+" and "-" across the mitochondrial inner membrane. When the transcription factor enters the nucleus target genes such as
hsp-60 are transcribed to respond to mitochondrial stress. FCCP is a protonophore that shuttles protons across the mitochondrial inner membrane resulting in decreased Δψm. B) Adult C. elegans are shown after treatment with TMRE, a potentiometric Δψm indicator. Quantification of fluorescence is shown below the representative images. From left to right, each bar represents the mean fluorescence from N = 17, 17, 8, 15, 16, 21, 11 animals. C) Adult C. elegans are shown expressing HSP-60::GFP. Control is compared to paraquat, a known UPRmt activator, and to FCCP treatment. Quantification is shown below the representative images. From left to right, each bar represents the mean fluorescence from N = 44, 42, 18, 42, 22, 28, 6, 33 animals. Raw fluorescence values are shown normalized to no treatment control in all cases. Scale bar is 250 μm in all images. Experimental N values are individual animals. Data were obtained across at least 3 different days. *p < 0.05 compared to control by one-way ANOVA with Bonferroni's test in all cases. Data are means + SEM.