Peroxisome Functions

Membrane-enclosed organelles involved in:

• β-oxidation of very-long-chain fatty acids (VLCFA) (strictly peroxisomal process)
• α-oxidation of branched-chain fatty acids (strictly peroxisomal process)
• Catabolism of amino acids and ethanol
• Synthesis of bile acids and plasmalogens (important membrane phospholipid, especially in white matter of brain)

Peroxisome Disorders

Zellweger syndrome—autosomal recessive disorder of peroxisome biogenesis due to mutated PEX genes. Hypotonia, seizures, jaundice, craniofacial dysmorphia, hepatomegaly, early death.

Refsum disease—autosomal recessive disorder of α-oxidation → buildup of phytanic acid due to inability to degrade it. Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia. Treatment: diet, plasmapheresis.

Adrenoleukodystrophy—X-linked recessive disorder of β-oxidation due to mutation in ABCD1 gene → VLCFA buildup in adrenal glands, white (leuko) matter of brain, testes. Progressive disease that can lead to adrenal gland crisis, progressive loss of neurologic function, death.

Proteasome

Barrel-shaped protein complex that degrades ubiquitin-tagged proteins. Defects in the ubiquitin-proteasome system have been implicated in some cases of Parkinson disease.

Cytoskeletal elements

A network of protein fibers within the cytoplasm that supports cell structure, cell and organelle movement, and cell division.

Microtubule Structure and Function

#boundingbox

Microtubules are cylindrical outer structures composed of a helical array of polymerized heterodimers of α- and β-tubulin. Each dimer has 2 GTP bound. They are incorporated into flagella, cilia, and mitotic spindles, and are also involved in slow axoplasmic transport in neurons.

Molecular motor proteins—transport cellular cargo toward opposite ends of microtubule:

• Retrograde transport to microtubule (+) → (−)—mediated by dynein.
• Anterograde transport to microtubule (−) → (+)—mediated by kinesin.

Interestingly, certain pathogens like Clostridium tetani toxin, herpes simplex virus, poliovirus, and rabies virus exploit dynein for retrograde transport to the neuronal cell body.

Drugs Affecting Microtubules

Drugs that act on microtubules (often by disrupting their construction):

• Mebendazole (antihelminthic)
• Griseofulvin (antifungal)
• Colchicine (antigout)
• Vinca alkaloids (anticancer)
• Taxanes (anticancer)

Remember, the negative end of a microtubule is typically near the nucleus, and the positive end points towards the periphery. Ready? Attack!

Topics Covered:

• Peroxisome Functions
• Peroxisome Disorders
• Proteasome and Cytoskeletal Elements Overview
• Microtubule Structure and Motor Proteins
• Drugs Affecting Microtubules