Lysosomes: recycling system of the cell
membrane enclosed organelles that consist of 50-60 hydrolytic enzymes most active at acidic pH:
capable of breaking down proteins, carbohydrates, lipids, and nucleic acids.
monomers escape through membrane and can be reused by cell
removes both material OUTSIDE the cell and obsolete components of the cell itself
morphologically diverse
Lysosomal Sorting Pathway: step 1
phosphorylation of lysosomal enzymes via mannose-6-phosphate
Lysosomal Sorting Pathway: step 2
binding of lysosomal enzyme to M6P receptor, followed by budding via clathrin coated pits
clathrin–adaptin–M6P receptor through membrane–M6P-L.Enzyme
Primary Lysosomes
enzymes inactive
storage site of lysosomal hydrolases
homogenous enzymes
Secondary Lysosomes
site of catalytic process
carries digestive enzymes
actively enzymatic
Pathways for intracellular degradation
- Receptor mediated endocytosis
- Autophagy
- Phagocytosis
Development of Lysosomes
Primary Lysosome buds from Golgi and fuses with an early endosome. Clathrin recycled.
Early endosome matures into Late endosome, secondary lysosome buds from late endosome
Lysosomes are formed from
fusion of transport vesicle with endosome
internal pH of late endosome =
5.5
Familial hypercholesterolemia
mechanism of cholesterol uptake is disrupted
elevation of LDL, the predominant cholesterol transport protein in plasma
Primary defect of hypercholesterolemia
defect in LDL receptor
Peroxisomes, also called
microbodies
Peroxisomes are a diverse group of organelles. They contain enzymes that ______ and which in turn can be broken down by ______
produce hydrogen peroxide
H2O2 is then broken down by catalase
function of the microbody (peroxisome)
hydrogen peroxide production
beta oxidation of long chain fatty acids
bile and cholesterol synthesis
detoxify alcohol
what do we “often” find in the core of the peroxisome
“urate oxidase” crystalline core
Peroxisome disorder
Zellweger spectrum disorder
peroxisome biogenesis disorder
12 genes required for peroxisome synthesis: defect in any one of these genes will result in disorders on the Zellweger Spectrum
Zellweger syndrome
absent or reduced number of peroxisomes in the cells
syndrome present in patients at birth, has no cure, causes dead within the first year of life
spaces in the mito
intermembrane space
cristae space
matrix
space mitochondria take up in the cell
around 20%
mitochondria are associated with what cellular skeletal system
microtubular cytoskeleton
Where are the mitochdonria the least dynamic and why
high energy cells: they are more “fixed”, and have to pack into tight spaces between myofibrils around flagellum of sperm cells
two associations of the mito in the cell talked about in class
mito associated with microtubular cytoskeleton
mito associated with ER (ER can cleave the mito)
3.75 billion years
first living cells
2 billion years
aerobic respiration becomes widespread
1 million years
first multicellular plants and animals
Evolutionary sequence leading to present day mito carrying eukaryote
an anaerobic prokaryote split into an anaerobic eukaryote and an aerobic prokaryote
eukaryote consumed the prokaryote
symbiosis
components of mtDNA
ATP Synthase subunits, NADH dehydrogenase subunits, cytochrome oxidases, cytochrome b,
Differences between the mitochondrial code and the “universal code”
UGA doesnt make STOP is makes Trp
AUA doesnt make Ile it makes Met
AGA/AGG doesn’t make Arg it makes STOP
200 diseases related to mitochondrial DNA defects. What do a large number of these diseases effect?
tRNA genes: often mutations prevent tRNA aminoacylation
UGA codes for ____ and ____ in universal vs mtDNA
STOP = universal Trp = Mt
AUA codes for _____ and _____ in universal vs mtDNA
Ile = universal Met = mt
AGA/AGG codes for _____ and _____ in universal vs mtDNA
Arg = universal STOP = mt
Mitochondrial DNA diseases can come from two places
either nucleus encoded or defects in mtDNA
Mother’s Curse
theory: susceptibility to mito disease come from mom. this allows male harming defects to accumulate in mitochondrial genomes: they may benefit women but harm the dudes
Mitochondrial DNA and Aging
accumulation of ROS-generated by the respiratory chain can cause mito damage
less efficient DNA replication and repair mechanisms
ROS increases with AGE: