Peroxisomes are remarkably responsive organelles. their malleability suggests complex mechanisms operate

Peroxisomes are remarkably responsive organelles. their malleability suggests complex mechanisms operate to control cellular dynamics and the specificity of cellular responses and functions extending well beyond the peroxisome itself. A deeper understanding of the functions of peroxisomes and the mechanisms that control their plasticity could offer opportunities for exploiting changes in peroxisome abundance to control cellular function. Introduction Peroxisomes are spherical compartments delimited by a single phospholipid bilayer and are found distributed throughout the cytoplasm of most eukaryotic cells. In most cell types investigated to date peroxisomes exhibit remarkable plasticity responding to various environmental stimuli to alter their size and number per cell and their metabolic functions [1]. Peroxisomes are formed by two separate and possibly complementary biogenesis pathways: budding from the endoplasmic reticulum (ER) and growth and division of existing peroxisomes [1 2 They possess a posttranslational protein translocation system termed the peroxisomal importomer [3] which imports exclusively fully folded and sometimes oligomeric protein complexes composed of enzymes destined for the peroxisomal matrix together with their peroxisome-targeting chaperone [4-6]. Peroxisomes are metabolically plastic which is due in part to the enzyme-mediated production of and protection from reactive oxygen species (ROS) and the broad specificity in substrates these oxidative reactions confer [7]. Beyond their metabolic functions and in alignment with an increasing recognition of the complexity and interconnectedness of various components of the cell peroxisomes are increasingly being revealed as hubs or platforms for signaling in their own right with roles critical for innate immunity development and differentiation [8]. Therefore the mechanisms controlling the plasticity of peroxisomes and the HPGDS inhibitor 1 formation of signaling complexes on peroxisomes offer exciting avenues for research. In this review we highlight recent findings from yeast and mammalian cells that reveal the coordinated control that gives rise to both the dynamic formation of peroxisomes and the signaling events carried out at the organelle. Peroxisomes – Control at the level HPGDS inhibitor 1 of transcription Factors involved in the biogenesis and proliferation of peroxisomes have been well conserved during evolution [9] and particularly since the divergence HPGDS inhibitor 1 of metazoan and fungal lineages some 1.5-1.2 billion years ago. genes encode proteins called peroxins that facilitate the varied aspects of the peroxisome life cycle including membrane protein Rabbit polyclonal to ISCU. targeting matrix protein targeting and translocation peroxisome division peroxisome movement and selected peroxisome turnover or pexophagy. This conservation in cellular pathways regulating peroxisomal biogenesis extends to the underlying transcriptional response to environmental and metabolic signals that initiate peroxisome proliferation. Ligand-mediated regulation of genes coding for peroxisomal proteins in the budding yeast starts with the fatty-acid-mediated activation of the oleate-activated transcription factor 1 and peroxisome induction pathway 2 (Oaf1/Pip2) heterodimer [10 11 Upon its binding to a fatty acid Oaf1 complexes with Pip2 to form a heterodimer which binds to DNA sequences known as oleate response elements located in the upstream promoter regions of many peroxisomal genes including itself. Similarly transcriptional regulation of peroxisomal genes in mammals was first discovered in rodent models where peroxisome proliferators such as fatty acids but also hypolipidemic drugs activate the peroxisome proliferator-activated receptor (PPAR) and retinoic acid receptor (RAR) family of nuclear receptors leading to the upregulation of expression of genes encoding peroxisomal proteins and the proliferation of peroxisomes [12 13 Closer examination of the kinetics of regulation of the Oaf1/Pip2 HPGDS inhibitor 1 and PPAR/RAR heterodimers revealed that they function as asymmetric positive feedback loops so named because ligand-mediated heterodimerization upregulates the expression.