[HTML][HTML] Cholesterol, lipid rafts, and disease

K Simons, R Ehehalt - The Journal of clinical investigation, 2002 - Am Soc Clin Investig
The Journal of clinical investigation, 2002Am Soc Clin Investig
Nonstandard abbreviations used: glycophosphatidylinositolanchored (GPI-anchored);
endothelial nitric oxide synthase (eNOS); β-secretase (BACE); endoplasmic reticulum (ER);
baby hamster kidney (BHK); detergent-resistant membranes (DRMs); Alzheimer disease
(AD); amyloid-β-peptide (Aβ). ma membrane. This increase seems to be achieved by
excluding lipid rafts from the retrograde traffic between the Golgi complex and the ER (8).
Thus, lipid rafts are moved forward from the Golgi complex to the plasma membrane, where …
Nonstandard abbreviations used: glycophosphatidylinositolanchored (GPI-anchored); endothelial nitric oxide synthase (eNOS); β-secretase (BACE); endoplasmic reticulum (ER); baby hamster kidney (BHK); detergent-resistant membranes (DRMs); Alzheimer disease (AD); amyloid-β-peptide (Aβ). ma membrane. This increase seems to be achieved by excluding lipid rafts from the retrograde traffic between the Golgi complex and the ER (8). Thus, lipid rafts are moved forward from the Golgi complex to the plasma membrane, where they concentrate but also spread into the endocytic recycling pathways (9). Cholesterol and sphingolipid concentrations are tightly regulated and limit the supply of lipid rafts to organelles supplied by the Golgi apparatus.
The cell pays a price for using cholesterol as a spacer for keeping rafts together. Cholesterol is toxic, and its cellular levels are kept in tight control by an intricate network of transcriptional regulation of cholesterol biosynthesis and cellular uptake as well as by deposition of cholesterol into fat droplets in an esterified form, and by cellular efflux (ref. 10; see also Tall et al.[ref. 11] and Tabas [ref. 12], this Perspective series). Disturbance of these tightly regulated processes leads to a variety of diseases of lipid metabolism, as shown in Table 1.
The Journal of Clinical Investigation