title: Peroxisomes are required for lipid metabolism and muscle function in Drosophila melanogaster.
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.
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Faust
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: Arvind
authors.initials: A
authors.lastname: Manisundaram
authors.affiliation: Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Pavlina T
authors.initials: PT
authors.lastname: Ivanova
authors.affiliation: Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Milne
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: James B
authors.initials: JB
authors.lastname: Summerville
authors.affiliation: Department of Pharmacology and the Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Wangler
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Stern
authors.affiliation: Department of Biochemistry and Cell Biology, Rice University, Houston, Texas, United States of America.
authors.forename: James A
authors.initials: JA
authors.lastname: McNew
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D050356:Lipid Metabolism; D009132:Muscles / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D020675:Peroxisomes / Q000378:metabolism*; D011679:Pupa / Q000502:physiology; D034622:RNA Interference
chemical_list: D029721:Drosophila Proteins