Cell Organelles

Cell Organelles

Which of the following is a characteristic of lysosomal storage disorders?

Lysosomal storage disorders form a group of about seventy rare inherited metabolic diseases sharing unifying pathophysiology despite diverse enzyme defects. Mutations in genes encoding lysosomal acid hydrolases, accessory activator proteins GM2 activator and saposins, sulfatases requiring formylglycine modification by SUMF1, or lysosomal integral membrane transporters such as cystinosin and sialin impair specific catabolic steps. Because residual enzyme activity falls below threshold, typically less than ten percent of normal, undegraded macromolecular substrates such as sphingolipids, mucopol

Ref: Parenti et al., Nature Reviews Drug Discovery 2015: Lysosomal Storage Disorders – Substrate Accumulation.

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Cell Organelles

The hydrolytic enzymes of lysosomes function best at pH:

Lysosomal acid hydrolases number about sixty different enzymes covering proteolysis, glycoside cleavage, lipid hydrolysis, nuclease activity and sulfatase action, each evolutionarily tuned for acidic environments to maximize substrate turnover and simultaneously protect cell from uncontrolled proteolysis if leakage occurs. Most display pronounced pH optima between 4.5 and 5.0, precisely matching steady-state lumen acidity maintained by vacuolar H+ ATPase delivering protons and chloride counter-transport via ClC-7 Cl-/H+ antiporter that prevents excessive voltage buildup. At this acidic pH cata

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: Lysosomal Acid Hydrolases – pH Optimum 4.5.

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Cell Organelles

Which pair of organelles have the same pH and ionic composition?

Ionic milieu of subcellular compartments reflects membrane permeability architecture and active pumping. The mitochondrial outer membrane contains abundant 19-stranded beta-barrel voltage-dependent anion channels, VDAC porins, present at high density allowing nonselective diffusion of solutes up to about 4 to 5 kilodaltons, including chloride, potassium, sodium, small metabolites, ATP, ADP, NADH and citrate. Because VDAC pores remain predominantly open under physiological low potentials, the intermembrane space equilibrates rapidly with cytosol via free diffusion, sharing near-identical pH aro

Ref: Nicholls & Ferguson, Bioenergetics, 4th ed., Chapter 3: Outer Membrane Permeability and Cytosol-Equilibrated Intermembrane Space.

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Cell Organelles

Endosomes are formed from:

Endosomal system is central node of vesicular traffic that integrates endocytic and biosynthetic routes to sort cargo after internalization or secretion. Classical early endosomes originate when clathrin-coated pits invaginate with assistance of AP2 adaptor, epsin and dynamin GTPase scission, or when caveolae containing caveolin internalize, delivering extracellular ligands, nutrient receptors such as transferrin receptor, signaling receptors like EGFR, and fluid-phase markers into cell. These primary vesicles rapidly lose coat through auxilin and Hsc70 and fuse homotypically via Rab5-GTP, EEA

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: Endosome Formation from Plasma Membrane and TGN.

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Cell Organelles

Which of the following is a membrane-bound organelle?

Eukaryotic cytoplasm contains membrane-bound and non-membrane organelles distinguished by presence of phospholipid bilayer enclosing aqueous compartment that allows compositional specialization. Ribosomes are 80S megaDalton protein-RNA assemblies consisting of small and large subunits that translate mRNA in cytosol or on rough endoplasmic reticulum, lacking membrane and exchanging subunits dynamically. Nucleolus is membraneless nuclear subdomain formed by liquid-liquid phase separation around rDNA repeats for ribosome biogenesis. Centrosome comprises two centrioles surrounded by pericentriolar

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 12: Peroxisomes as Single Membrane-Bound Organelles.

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Cell Organelles

Which of the following statements is false regarding peroxisomes?

Peroxisomes are single-membrane organelles morphologically and functionally distinct from lysosomes despite both participating in degradative metabolism. Transmission electron microscopy shows spherical vesicles 0.1 to 1 micrometer with electron-dense crystalline cores composed of urate oxidase in rat or dense catalase aggregates in humans. Unlike double-membrane mitochondria and nucleus, peroxisomes are bounded by single phospholipid bilayer enriched in peroxisomal membrane proteins PMP70, ALDP, PEX11 isoforms and containing import translocon. Their matrix contains oxidative enzymes such as a

Ref: Smith & Aitchison, Cold Spring Harbor Perspect Biol 2013: Peroxisomes Originate from ER and Contain Oxidases.

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Cell Organelles

Which disorder is associated with peroxisomal dysfunction?

Peroxisome biogenesis requires more than thirty PEX genes encoding peroxins that mediate membrane protein targeting, matrix protein import, proliferation and inheritance. Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease constitute Zellweger spectrum, recognized as prototypical peroxisomal biogenesis disorders inherited autosomal recessively with combined incidence about 1 in 50,000. Most commonly mutations in PEX1, PEX6, PEX26 members of AAA ATPase complex that recycles PEX5 receptor block both PTS1 and PTS2 import pathways, leading to cytosolic mislocalization of

Ref: Steinberg et al., Biochimica et Biophysica Acta 2006: Zellweger Syndrome and Peroxisome Biogenesis Disorders.

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Cell Organelles

Which enzyme in peroxisomes detoxifies H₂O₂?

Because peroxisomal oxidases produce stoichiometric hydrogen peroxide during oxidation of fatty acids, urate, D-amino acids and polyamines, cells require robust detoxification to prevent oxidative damage to proteins, lipids and DNA. Catalase is the signature antioxidant enzyme residing in peroxisomal matrix, often forming electron-dense crystalline core visible by electron microscopy in rat liver. It is a 240 kDa heme-containing homotetramer that disproportionates hydrogen peroxide into water and molecular oxygen with extremely high turnover number near ten million molecules per second, one of

Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 12: Peroxisomes and Catalase Function.

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Cell Organelles

What is the major function of peroxisomes?

Peroxisomes are ubiquitous single-membrane organelles present in most eukaryotes central to lipid metabolism, ROS balance, and signaling. Their hallmark metabolic function is beta-oxidation of very-long-chain fatty acids longer than 22 carbons, branched-chain fatty acids like phytanic acid requiring alpha-oxidation first, and polyunsaturated fatty acids that mitochondria cannot handle efficiently due to double bond positions. Unlike mitochondrial beta-oxidation coupled to electron transfer flavoprotein and respiratory chain to produce ATP, peroxisomal acyl-CoA oxidases, ACOX1, ACOX2, ACOX3, tr

Ref: Wanders & Waterham, Annual Review of Biochemistry 2016: Peroxisome Biogenesis and Fatty Acid Beta-Oxidation.

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Cell Organelles

Gaucher’s disease is caused by a deficiency of:

Gaucher disease, the most common lysosomal storage disorder with incidence about 1 in 40,000 to 60,000 in general population and 1 in 800 among Ashkenazi Jews, arises from autosomal recessive mutations in GBA1 gene on chromosome 1q21 encoding lysosomal glucocerebrosidase, also called acid beta-glucosidase or glucosylceramide beta-glucosidase. This membrane-associated enzyme normally cleaves glucosylceramide, a major membrane glycosphingolipid intermediate, into ceramide and glucose within lysosomes of macrophages that recycle membranes from phagocytosed senescent erythrocytes and leukocytes. D

Ref: Scriver et al., The Metabolic and Molecular Bases of Inherited Disease, Chapter 146: Gaucher Disease – Glucocerebrosidase.

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Cell Organelles

Which lysosomal enzyme degrades complex polysaccharides?

Lysosomal lumen houses a consortium of about sixty acid hydrolases tailored to distinct macromolecular classes, all evolutionarily optimized for acidic pH and limited activity at neutral pH to protect cell. Among them, glycosidases or glycoside hydrolases hydrolyze glycosidic linkages in oligosaccharides, N-linked glycoproteins, glycolipids and glycosaminoglycans. Examples include acid alpha-glucosidase removing alpha-1,4 linkages in glycogen, beta-galactosidase cleaving galactose from GM1 ganglioside, alpha-mannosidase, neuraminidase, fucosidase, and hexosaminidases A and B that degrade GM2 g

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 13: Lysosomal Hydrolases – Glycosidases.

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Cell Organelles

Which lysosomal membrane protein is required for fusion with phagosomes?

Phagosome maturation in macrophages and neutrophils converts a nascent bacteria-containing vacuole into a microbicidal phagolysosome through sequential interactions with early endosomes, late endosomes and terminal lysosomes. Acquisition of lysosomal membrane proteins marks progression, with lysosome-associated membrane proteins 1 and 2, LAMP1 and LAMP2, being the most abundant heavily glycosylated proteins delivered to maturing phagosomes, protecting membrane from hydrolases. Studies using LAMP-1 and LAMP-2 knockout mice and combined siRNA show single loss causes mild delay while double defic

Ref: Huynh et al., EMBO Journal 2007: LAMP Proteins Are Required for Fusion of Lysosomes with Phagosomes.

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