title: The proteome of human liver peroxisomes: identification of five new peroxisomal constituents by a label-free quantitative proteomics survey.
abstract: The peroxisome is a key organelle of low abundance that fulfils various functions essential for human cell metabolism. Severe genetic diseases in humans are caused by defects in peroxisome biogenesis or deficiencies in the function of single peroxisomal proteins. To improve our knowledge of this important cellular structure, we studied for the first time human liver peroxisomes by quantitative proteomics. Peroxisomes were isolated by differential and Nycodenz density gradient centrifugation. A label-free quantitative study of 314 proteins across the density gradient was accomplished using high resolution mass spectrometry. By pairing statistical data evaluation, cDNA cloning and in vivo colocalization studies, we report the association of five new proteins with human liver peroxisomes. Among these, isochorismatase domain containing 1 protein points to the existence of a new metabolic pathway and hydroxysteroid dehydrogenase like 2 protein is likely involved in the transport or β-oxidation of fatty acids in human peroxisomes. The detection of alcohol dehydrogenase 1A suggests the presence of an alternative alcohol-oxidizing system in hepatic peroxisomes. In addition, lactate dehydrogenase A and malate dehydrogenase 1 partially associate with human liver peroxisomes and enzyme activity profiles support the idea that NAD(+) becomes regenerated during fatty acid β-oxidation by alternative shuttling processes in human peroxisomes involving lactate dehydrogenase and/or malate dehydrogenase. Taken together, our data represent a valuable resource for future studies of peroxisome biochemistry that will advance research of human peroxisomes in health and disease.
authors: Department of Molecular Genetics and Cell Biology, Ulm University, Ulm, Germany.
authors: Thomas
authors: T
authors: Gronemeyer
authors: Sebastian
authors: S
authors: Wiese
authors: Rob
authors: R
authors: Ofman
authors: Christian
authors: C
authors: Bunse
authors: Magdalena
authors: M
authors: Pawlas
authors: Heiko
authors: H
authors: Hayen
authors: Martin
authors: M
authors: Eisenacher
authors: Christian
authors: C
authors: Stephan
authors: Helmut E
authors: HE
authors: Meyer
authors: Hans R
authors: HR
authors: Waterham
authors: Ralf
authors: R
authors: Erdmann
authors: Ronald J
authors: RJ
authors: Wanders
authors: Bettina
authors: B
authors: Warscheid
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D008099:Liver / Q000378:metabolism*; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D013194:Staining and Labeling
chemical_list: D020543:Proteome