title: Thematic review series: lipid posttranslational modifications. Lysosomal metabolism of lipid-modified proteins.
abstract: Much is now understood concerning the synthesis of prenylated and palmitoylated proteins, but what is known of their metabolic fate? This review details metabolic pathways for the lysosomal degradation of S-fatty acylated and prenylated proteins. Central to these pathways are two lysosomal enzymes, palmitoyl-protein thioesterase (PPT1) and prenylcysteine lyase (PCL). PPT1 is a soluble lipase that cleaves fatty acids from cysteine residues in proteins during lysosomal protein degradation. Notably, deficiency in the enzyme causes a neurodegenerative lysosomal storage disorder, infantile neuronal ceroid lipofuscinosis. PCL is a membrane-associated flavin-containing lysosomal monooxygenase that metabolizes prenylcysteine to prenyl aldehyde through a completely novel mechanism. The eventual metabolic fates of other lipidated proteins (such as glycosylphosphatidylinositol-anchored and N-myristoylated proteins) are poorly understood, suggesting directions for future research.
authors.affiliation: Hamon Center for Therapeutic Oncology Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: Jui-Yun
authors.initials: JY
authors.lastname: Lu
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008247:Lysosomes / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D009227:Myristic Acids / Q000737:chemistry / Q000378:metabolism; D017368:Protein Prenylation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013869:Thiolester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D009227:Myristic Acids; D011506:Proteins; C108083:prenylcysteine lyase; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D013437:Carbon-Sulfur Lyases