Abstract
Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in part by neuronal dysfunction, craniofacial malformations, and low muscle tone (hypotonia). These devastating diseases lack effective therapies and the development of animal models may reveal new drug targets. We have generated Drosophila mutants with impaired peroxisome biogenesis by disrupting the early peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER and peroxisomal membrane protein localization. pex3 deletion mutants lack detectible peroxisomes and die before or during pupariation. At earlier stages of development, larvae lacking Pex3 display reduced size and impaired lipid metabolism. Selective loss of peroxisomes in muscles impairs muscle function and results in flightless animals. Although, hypotonia in PBD patients is thought to be a secondary effect of neuronal dysfunction, our results suggest that peroxisome loss directly affects muscle physiology, possibly by disrupting energy metabolism. Understanding the role of peroxisomes in Drosophila physiology, specifically in muscle cells may reveal novel aspects of PBD etiology.
Highlights
Peroxisomes are small, spherical, single-membrane bound organelles found in almost all eukaryotic cells
We expanded the tissues examined, focusing primarily on larval tissues involved in energy metabolism: the gut, fat body, oenocytes, body wall muscles, and the epidermis
We examined the effect of Pex3 loss on peroxisome biogenesis
Summary
Peroxisomes are small, spherical, single-membrane bound organelles found in almost all eukaryotic cells. Peroxisome Membrane Biogenesis The formation of a mature, metabolically active peroxisome depends on the activity of Peroxin (Pex) proteins [3]. Peroxisomes can form de novo from the endoplasmic reticulum (ER) or divide autonomously from pre-existing organelles. Pex is a peroxisomal membrane protein (PMP) that is required for de novo production from the ER as well as for ongoing membrane protein import from the cytosol [4,5,6,7,8]. During de novo organelle biogenesis, newly synthesized Pex localizes to the ER, concentrates into foci, and is carried away from the ER in buds that mature into peroxisomes [4]. In addition to the de novo biogenesis pathway, existing peroxisomes can grow and divide [12]
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