Thematic review series: lipid posttranslational modifications. Lysosomal metabolism of lipid-modified proteins.
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.
Lu
Jui-Yun
JY
Hamon Center for Therapeutic Oncology Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
Hofmann
Sandra L
SL
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
D017261:Glycosylphosphatidylinositols; D009227:Myristic Acids; D011506:Proteins; C108083:prenylcysteine lyase; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase; D013437:Carbon-Sulfur Lyases