lysosomes

which cells contain lysosomes

all but RBCs

why are lysosomes visible by EM

have dense protein rich core

role of lysosomes

degredative compartment

role in apoptosis

can repair plasma memb damage

act as secretory vesicles in imune cells

how are mols delivered to lysosomes

endocytosis and autophagy

what happens to the digestion products of lysosomes

translocated into cytosol via secondary active transporters (transp H+ into lumen)

how is lysosomal pH maintained

vacuolar proton pump (vATPase) pump H+ into lumen

req ATP

what mols are endocytosed

specific mols via receptor binding (LDL via LDL receptor)

receptors can be endocytosed (EGF receptor)

or nonspecifically

pathway of endocytosed mols

into early endosomes

mature into late that fuse with lysosomes

define autophagy

removal of cytoplasmic compoents for degred by lysosomes eah

what are the 3 types of autophagy

macroautophagy

chaperone mediated autophagy

microautophagy

macrophagy

removes old organelles, aggregates, long lived proteins

envelopemtn of cyto mat by autophagosome

(surrounded by memb from ER, p memb or mito)

autophagosomes fuse with lysosomes

function of activated caspases (cyto proteases)

act on cellular tagets to induce apoptosis

waht do caspases cause

release of cathepsins (lyso proteases) into cyto sol where they act

function of cathepsins in cyto

cleave proteins

trigger mitochondrial/ intrinsic pathway of apoptosis via Bid

are lysosomes necessary for apoptosis

no, just amplify process

how do lysosomes act in p memb repair

mechanically stressed cells get damaged and lysosomes act as a memb reserve to repair (exocytosis of lysosomes to damage site) triggered by Ca2+ influx (det by synaptotagmin 7)

lysosomal storage diseases

defects in degradative function of lysosomes (accumulate in lysosome often)

cause of lysosomal storage diseases

defective hydrolase trafficking to lysosomes

poor activity of hydrolases

poor activity of lysosomal transporters

I cell disease

mut in gene encoding N-acetylglucosamine-1-phosphotransferase

cause of i cell disease

cant form m6p tag in golgi therefore cant transport to lysosomes (things get exocytosed instead)

what causes dissoc of M6P protein from M6P receptor in lysosome

acidic pH

Pompe disease

affects alpha d glucosidase

some glycogen in lysosome which needs hydrolysed to transp out (therefore accumulate)

treatment of Pompe disease

Enzyme replacement therapy

Fabry disease

mut in alpha galactosidase that removes terminal galactose from Gb3 there it accumulates in lysosomes

treatment of fabry disease

ERT

migalastat (stabilises mutant alpha galactosidase allowing not to be degraded by ERAD, drug dissoc in lyso due to low pH)

Infantile sialic acid storage disease and salla disease

sialin is a lyso memb tranp for degrad products into cyto

muts in sialin cause sialic acids to accumulate

ISASD cause activity abolished or ERAD and salla cause reduced activity