Lysosomes & Peroxisomes - Medical Microanatomy Flashcards

Flashcards covering lysosome structure, function, trafficking, endocytosis, autophagy, lysosomal storage diseases, exocytosis, proteasomes, and peroxisomes (structure, import, disorders, and clinical relevance) based on lecture notes.

What is the primary function of lysosomes?

Major site of intracellular digestion of macromolecules, accomplished enzymatically by acid hydrolases.

What targeting signal directs lysosomal enzymes to lysosomes?

Mannose-6-phosphate (M6P) tag.

From which organelle are lysosomes derived?

Golgi apparatus (lysosomes originate from the Golgi after enzymes are processed in the secretory pathway).

Name four safety features that prevent autodigestion by lysosomes.

Lysosome membrane separates enzymes from cytoplasm; interior pH is acidic; heavy glycosylation of lysosomal enzymes and membrane proteins; unusual lipid in the lysosomal membrane that resists degradation.

Which lysosome-related structures can be identified by electron microscopy?

Multivesicular bodies, autophagic lysosomes, and residual bodies containing lipofuscin.

Which histochemical method is commonly used to identify lysosomal enzymes?

Acid phosphatase histochemistry (acid phosphatase assay with lead phosphate precipitation).

What are the two main pathways for delivering lysosomal enzymes to lysosomes?

The mannose-6-phosphate (M6P) pathway and the M6P-independent pathway.

Outline the mannose-6-phosphate targeting pathway from the Golgi to the lysosome.

Enzymes synthesized in the ER are transported to the Golgi, where they are tagged with M6P; M6P receptors in the Golgi bind these enzymes; clathrin-coated vesicles bud off and deliver them to the lysosome/endosome; in acidic endosomes, enzymes dissociate from the M6P receptor and become activated; receptors are recycled to the Golgi.

What are the sources of material digested by lysosomes?

Heterophagy (external materials via endocytosis), Autophagy (cell’s own cytoplasm), and Crinophagy (stored secretory material).

What are the forms of endocytosis?

Phagocytosis, pinocytosis, and receptor-mediated endocytosis.

What are the possible fates of endocytosed material?

Recycling back to the plasma membrane, transcytosis across the cell, or degradation within lysosomes.

Through which endosomal stages does endocytosed material typically pass on its way to lysosomes?

Early endosomes → multivesicular bodies (MVBs) → late endosomes → lysosomes.

Describe receptor-mediated endocytosis steps using LDL as an example.

LDL binds its receptor and clusters into a clathrin-coated pit; vesicle forms and sheds its coat; fuses with an early sorting endosome; ligands dissociate from receptors; receptors recycle back to the membrane; materials are delivered to lysosomes.

What is autophagy and its significance?

Self-digestion: cytoplasmic proteins and organelles degraded by lysosomes; macroautophagy involves autophagosomes that fuse with lysosomes; important for turnover and stress responses.

What are the three types of autophagy?

Macroautophagy, Microautophagy, and Chaperone-mediated autophagy.

What is crinophagy?

Digestion of stored secretory material by the cell that produced it; fusion of secretory vacuoles with lysosomes.

Lysosomal storage diseases: what are the two main defect types?

1) Defects in a gene encoding a lysosomal hydrolase enzyme (e.g., Tay-Sachs, metachromatic leukodystrophy, Hurler’s disease). 2) Defects in processing that lead to mis-sorting of lysosomal enzymes (e.g., I-cell disease).

Tay-Sachs disease: which enzyme is deficient and what accumulates?

Deficiency of β-hexosaminidase A; accumulation of GM2 ganglioside.

I-cell disease: what is the key defect?

Failure to create the mannose-6-phosphate marker on lysosomal enzymes, resulting in secretion of enzymes instead of targeting to lysosomes.

Exocytosis of lysosomes: what is its role and a notable example?

Lysosomal secretion to eliminate indigestible debris; notably used by osteoclasts during bone resorption.

What is the role of proteasomes in cytoplasmic degradation?

Degradation of damaged or misfolded proteins in the cytosol; proteins are tagged with ubiquitin (ubiquitinylation) to target them for proteasomal digestion.

What are peroxisomes and their general function?

Cytoplasmic organelles with a single membrane that oxidize lipids and detoxify toxins; generate hydrogen peroxide (H2O2) via oxidases; detoxify with catalase; involved in ethanol metabolism and plasmalogen synthesis for myelin.

What is the peroxisomal marker enzyme?

Catalase.

How are peroxisomal proteins imported? targeting signals and receptors.

Peroxisomal targeting signals (PTS) on proteins bind cytosolic receptors (e.g., Pex5); docking at the peroxisome membrane via docking proteins (Pex13/Pex14/Pex17); translocation into the peroxisome; receptors are recycled or degraded by ubiquitination.

Where does the peroxisomal membrane originate?

From the endoplasmic reticulum; most peroxisomal proteins are imported from the cytosol; peroxisomes can divide or form de novo.

Peroxisomal disorders: what are the major classes and examples?

Class 1: Zellweger syndrome and neonatal adrenoleukodystrophy (NALD) – lacking both N- and C-terminal targeting signals. Class 2: rhizomelic chondrodysplasia (lacks only N-terminal signal). Class 3: X-linked adrenoleukodystrophy (ALD) – defective transport of substrate into peroxisomes.

What are peroxisomal proliferators and their potential risk?

Substances (fatty acids, aspirin, certain drugs, industrial chemicals) that increase peroxisome numbers and oxidative capacity; may cause oxidative damage if catalase does not increase proportionally, potentially contributing to cancer.

Why are peroxisomes important for nervous system function?

Peroxisomes synthesize plasmalogen, a major phospholipid in myelin; many peroxisomal disorders affect the nervous system.

What is the role of plasmalogen in myelin and where is it formed?

Plasmalogen is a major phospholipid in myelin; its formation involves peroxisomal enzymes.

What is the key product of peroxisomal beta-oxidation and its significance?

Short- to long-chain fatty acids are oxidized to acetyl-CoA (and H2O2 is produced and detoxified); peroxisomes are especially involved in very long-chain fatty acids.