Lecture 5 - Exam 4: Autophagy and Endocytosis Flashcards
Organization of the Lysosome:
For the lysosome to maintain the acidic pH, what has to happen?
What does this require?
A proton pump in the lysosomal membrane actively transports protons into the lysosome.
Thus, pumping requires expenditure of energy in the form of ATP.
How much higher is the H+ concentration inside the lysosome than in the cytosol?
Hundredfold higher.
Most lysosomal enzymes are…?
Acid hydrolases
How are lysosomes formed?
Through a maturation process: Endosomal maturation.
During endosomal maturation, what decreases?
pH
What happens during endosomal maturation?
The early endosomes undergo a maturation process that ultimately results in the formation of the endolysosome, a temporary hybrid organelle resulting from fusion with lysosomes.
What are early endosomes (EE)?
-Recognized as the main sorting station in the endocytic pathway.
-Close to the cell membrane (energetically favorable).
-Heterogenous structure: relatively small.
-Rab5 that defines the early endosome, involved in “uncoating” and fusion.
-Weakly acidic - pH 5.9-6.8 (overall goal digestion, first step).
What are late endosomes (LE)?
-More circular but varies in size (no restriction).
-Multivesicular bodies (from multiple early endosomes fusing together).
-Rab7 identifies LE membranes.
-Slightly acidic pH 4.6-6.0 (more acidic as we get closer to lysosome)
What are endolysosomes?
Fusion compartment between the late endosome and the lysosome.
-It is the site of hydrolysis of most endocytic cargo.
Why are LEs subject to such a dramatic transformation?
-Exchange of membrane components (compartment conversion)
-Exchange of Rab proteins
-Movement to the perinuclear area
-A decrease in luminal pH
-Addition of LYSOSOMAL components
Describe acidification during maturation of late endosomes (LE).
-Vacuolar-type H+ ATPase (V-ATPase).
-Active transport of ATP
-Hydrogen ions passing through the channel complex drop the pH inside the compartment as it matures. During maturation the number of pumps increases.
What is the lysosomal storage disease?
Gaucher Disease
What is Gaucher disease?
-The most common of the lysosomal storage diseases.
-Caused by deficiency of glucocerebrosidase, which catalyzes hydrolysis of glucosylceramide to glucose and ceramide.
What are the symptoms of Gaucher Disease?
Impaired olfaction and cognition.
-Bone abnormalities.
-Rapid and premature destruction of blood cells, leads to anemia.
How are autophagosomes formed?
Regions of the cytoplasm or internal organelles (such as mitochondria) are enclosed by membranes derived from the endoplasmic reticulum, forming autophagosomes.
