Biogenesis, Structure and Function of Lysosomes
619
IGF
insulin-like growth factor
LAMP
lysosome-associated membrane protein
LIMP
lysosomal integral membrane protein
M6P
mannose 6-phosphate
M6PR
mannose 6-phosphate receptor
MVB
multivesicular body
NSF
N
-ethylmaleimide sensitive factor
PI
phosphotidylinositol
PI3P
phosphotidylinositol-3-phosphate
Rab
ras-related GTPase
t-SNARE
target membrane soluble
N
-ethylmaleimide sensitive attachment receptor
V-ATPase
Vacuolar proton-pumping ATPase
Vam3p
a t-SNARE in yeast
Vid
Vacuolar import and degradation
Vps
vacuolar protein sorting
v-SNARE
vesicle membrane soluble
N
-ethylmaleimide sensitive attachment receptor
Ā„
Lysosomes are organelles that are surrounded by a single membrane and contain
many hydrolases that are most active at an acidic pH. The pH within the lysosomal
lumen is usually maintained between 5.0 and 5.5 by a multisubunit, proton-pumping
ATPase in the lysosomal membrane of mammalian cells and in the vacuolar
membrane of yeast. Other organelles having some of the properties of lysosomes
include late endosomes and multivesicular bodies. However, these organelles have
protein and lipid constituents at least partially distinct from lysosomes.
Enzymes in the lysosomal lumen are targeted to that location by mannose
6-phosphate (M6P) carbohydrate modiĀ±cations in the case of mammalian cell
lysosomes or by linear peptide sequences for the yeast vacuole. Integral membrane
proteins within the lysosomal and vacuolar membranes are targeted to that location
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eptide motifs in cytosolic regions of the
proteins. These motifs interact with vesicle coat protein complexes that concentrate
the proteins into vesicles destined for fusion with lysosomes. Peripheral lysosomal
membrane proteins generally interact strongly with one or more integral membrane
proteins and/or lipids.
Lysosomes account for 1 to 15% of cell volume and of cell protein in mammalian
cells and 30 to 90% of cell volume in fungal and plant cells. This variability
depends on cell type and physiological status. The morphological appearance of
lysosomes also varies from vesicular to a more complex tubular lattice. Lysosomes
are responsible for degrading both extracellular and intracellular proteins as well as
other macromolecules.
The role of lysosomes in overall intracellular protein degradation depends on the
cell type and nutritional conditions. Lysosomes are responsible for most protein
degradation in liver and kidney, and certain lysosomal pathways of proteolysis are
activated in response to nutritional deprivation. On the other hand, lysosomes play a
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