Independence of triacylglycerol-containing compartments in cultured fibroblasts from Wolman disease and multisystemic lipid storage myopathy.
The functional relationship between the two subcellular compartments involved in catabolism of triglycerides, i.e. lysosomes and lipid-containing cytoplasmic vacuoles, has been investigated using cultured fibroblasts from patients affected with two different genetic lipid (triacylglycerol) storage disorders: Wolman disease and multisystemic lipid storage myopathy. As shown by metabolic studies in intact cultured cells, lysosomal degradation of exogenous labelled triacylglycerols (incorporated into lipoproteins and internalized via the apo B/E receptor pathway) was blocked in Wolman cells, whereas catabolism of endogenously biosynthesized triacylglycerols was in the normal range. In contrast, in fibroblasts from multisystemic lipid storage myopathy, the degradation of endogenous triacylglycerols was blocked, whereas that of exogenous triacylglycerols (i.e. from lipoproteins) was normal. This comparative study demonstrates that the lysosomal and cytoplasmic compartments are functionally independent. Enzymatic studies allows one to discriminate clearly between 3 lipases and 2 carboxylesterases the role of which is discussed.
Salvayre
R
R
Laboratoire de Biochimie, Faculté de Médecine, Université Paul Sabatier, Toulouse, France.
Nègre
A
A
Radom
J
J
Douste-Blazy
L
L
D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008052:Lipid Metabolism, Inborn Errors / Q000378:metabolism*; D009135:Muscular Diseases / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D014304:Triolein / Q000378:metabolism; D015223:Wolman Disease / Q000378:metabolism*
D014280:Triglycerides; D014304:Triolein