Bevington 4 cell turnover Flashcards
Protein degradation by
proteases
RNA degradation by
RNAses
DNA turnover (repair) by
Excision nucleases etc
Lipid degradation (lipolysis) by
Lipases etc
Autophagy-
- “self-eating”
Membrane vesicles fuse & accumulate (nucleation & extension) autophagosome forms to engulf a piece of cytoplasm (including organelles).
An organelle bounded by a double membrane forms transiently only for autophagy
-Mitochondria & endoplasmic reticulum may be source of autophagosome’s double membrane
Lysosomes
part of endosomal compartment of animal cells, degrading intracellular components & material endocytosed from outside.
Cell proteins constantly recycled -in organelles
(e.g. lysosomal & autophagosomal proteases max at low pH)
Cell proteins constantly recycled - in the cytosol
a) Calcium-activated cytosolic proteases (Calpains), neutral pH
b) Ubiquitin-proteasome pathway (UPP) – major contributor to total cellular protein turnover
Ubiquitin:
Ubiquitin small protein (76 AA residues) covalently attached to proteins targeted for degradation (e.g. Mis-folded proteins)
Proteasome
huge macro-molecular cylindrical complex in cytosol, contains “unfoldases” & proteases => degrades polyubiquitinated proteins
poly-ubiquitin chain is needed as marker for
proteasomal degradation, UPP 3 = sets of enzymes: E1, E2 and E3
WHY TURNOVER?
1) To control the time course of gene expression
Proteins and the mRNAs encoding them may need to be turned “on” and “off” in the cell
2) Proteins may “mis-fold”
3) Cumulative damage to the molecules
Reactive oxygen species (ROS):
cause damage to mis-fold proteins, DNA, Oxidised lipids
- “bi-product” of electron transport & oxidative phosphorylation in mitochondria
- high energy radiation (e.g. ultra-violet)
- inflammatory cells of immune system e.g. neutrophils
Ribonucleases (RNases):
enzymes that degrade mRNA
Lipid Peroxidation
Some Oxidised molecules not degraded & replaced
⇨ oxidised lipids in atherosclerosis=> heart disease