Peroxisomal Biogenesis: Genetic Disorders Reveal the Mechanisms

Peroxisomes are small and abundant membrane-bound organelles that contain enzymes for a variety of metabolic functions, including ß-oxidation of fatty acids, synthesis of plasmalogens and bile acids, and H2O2 production (1, 2). A group of human genetic diseases involves peroxisomal disorders (3) derived from two type of alterations: i) defects in a single peroxisomal enzyme, as found in X-Linked Adrenoleukodystrophy and Acatalasemia; and ii) Peroxisome Biogenesis Disorders (PBDs), which include the Zellweger’s Syndrome (ZS). Intense research has been devoted for decades to understand the mechanisms of biogenesis and maintenance of peroxisomes. Despite the paramount progress, there are still enigmatic aspects, specially regarding the pathways followed by peroxisomal membrane proteins and the origin of peroxisomal membrane precursors (2). Here we give an overview of the evidence that involves the endoplasmic reticulum (ER) from the most important genetic tools in the field: fibroblast cultures derived from Zellweger patients and yeast mutants.