The dynamics of peroxisome proliferation and species-specific transcriptional control of peroxisome biogenesis. (A) Saccharomyces cerevisiae cells expressing Pot1-GFP, a peroxisomal protein, were imaged after 2 and 20 h of oleic acid induction. Peroxisome number and size increase markedly over time, reflecting transcriptional activation of the biogenic program. Image area: 30 × 30 μm. Reproduced from Saleem et al. (2008). (B) Transmission electron micrographs of rodent hepatocytes under basal conditions (left) and after treatment with the peroxisomal proliferator Wy-14,643 (right), showing robust induction of peroxisome proliferation. Modified from (Reddy, 2004), with permi. (C) Immunofluorescence microscopy of huh7 cells treated with 4-phenylbutyrate (4-PBA) or mock (DMSO) control. Peroxisomes (green) are markedly increased in number following 4-PBA treatment. Image area: 16 × 16 μm. (D–F) Transcriptional circuits regulating peroxisome abundance in yeast and rodents and adipocyte differentiation in humans. Altered from Ratushny et al. (2012). (D) In yeast, fatty acids activate Oaf1, which heterodimerizes with Pip2 to induce expression of peroxisomal genes. (E) In rodents, the hypolipidemic drug clofibrate activates PPARα, which forms a heterodimer with RXRα to stimulate transcription of peroxisomal genes. (F) In humans, oxidized lipids activate PPARγ, which dimerizes with RXRα to primarily regulate the expression of genes involved in adipogenesis; PPARγ activation does not robustly drive peroxisome biogenesis.