Pathogenesis of cell injury – ribosome damage MCQs With Answer

Pathogenesis of cell injury – ribosome damage MCQs With Answer

The pathogenesis of cell injury due to ribosome damage is crucial for B. Pharm students studying molecular mechanisms of toxicity and disease. Ribosomal dysfunction—caused by oxidative stress, ribotoxins (e.g., ricin, Shiga toxin), antibiotics, or impaired ribosome biogenesis—leads to defective protein synthesis, activation of the unfolded protein response, and disturbed proteostasis. Consequences include apoptosis, necrosis, impaired cell repair, and organ-level toxicity. Understanding signaling pathways such as eIF2α phosphorylation, PERK activation, ribophagy, and translational arrest helps predict drug-induced adverse effects and design safer therapeutics. This focused review emphasizes mechanisms, detection methods, and clinical relevance in pharmacology. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which of the following directly inactivates ribosomes by depurinating 28S rRNA?

  • Ricin
  • Aminoglycosides
  • Cycloheximide
  • Chloramphenicol

Correct Answer: Ricin

Q2. Damage to ribosomes primarily impairs which cellular process?

  • DNA replication
  • Protein synthesis
  • Glycolysis
  • Membrane transport

Correct Answer: Protein synthesis

Q3. Which cellular response is activated by accumulation of misfolded proteins due to ribosomal dysfunction?

  • Inflammasome assembly
  • Unfolded protein response (UPR)
  • MAP kinase silencing
  • Ferroptosis

Correct Answer: Unfolded protein response (UPR)

Q4. Phosphorylation of eIF2α during ribosomal stress leads to:

  • Increased global translation
  • Translational arrest
  • Enhanced ribosome biogenesis
  • Immediate DNA repair

Correct Answer: Translational arrest

Q5. Which toxin causes ribosomal misreading by binding the 30S subunit in bacteria?

  • Aminoglycosides
  • Ricin
  • Shiga toxin
  • Actinomycin D

Correct Answer: Aminoglycosides

Q6. Ribophagy refers to:

  • Ribosome biogenesis in nucleolus
  • Autophagic degradation of ribosomes
  • Translation initiation complex assembly
  • Export of ribosomal subunits

Correct Answer: Autophagic degradation of ribosomes

Q7. Which pathway links ER stress from misfolded proteins to apoptosis?

  • PERK-eIF2α-CHOP pathway
  • mTORC1 activation
  • PI3K-Akt survival pathway
  • NF-κB canonical pathway

Correct Answer: PERK-eIF2α-CHOP pathway

Q8. Which antibiotic inhibits eukaryotic 80S ribosomes by blocking translocation?

  • Cycloheximide
  • Gentamicin
  • Tetracycline
  • Streptomycin

Correct Answer: Cycloheximide

Q9. Oxidative damage to ribosomal RNA typically results in:

  • Enhanced translation fidelity
  • Ribosomal stalling and mistranslation
  • Faster ribosome recycling
  • Increased ribosome synthesis

Correct Answer: Ribosomal stalling and mistranslation

Q10. Which cellular organelle’s dysfunction often exacerbates ribosome-related cell injury via ATP depletion?

  • Lysosome
  • Mitochondrion
  • Peroxisome
  • Golgi apparatus

Correct Answer: Mitochondrion

Q11. Shiga toxin inhibits protein synthesis by targeting which component?

  • 28S rRNA of the 60S subunit
  • tRNA charging enzymes
  • mRNA cap structure
  • Ribosomal protein S6

Correct Answer: 28S rRNA of the 60S subunit

Q12. Defects in ribosomal biogenesis often activate which tumor suppressor protein?

  • NFAT
  • p53
  • STAT3
  • HIF-1α

Correct Answer: p53

Q13. Which assay is commonly used to measure global protein synthesis in cells?

  • Comet assay
  • Puromycin incorporation (SUnSET)
  • TUNEL assay
  • ELISA for ATP

Correct Answer: Puromycin incorporation (SUnSET)

Q14. Which process clears misfolded proteins when proteasome capacity is exceeded during ribosomal stress?

  • Autophagy
  • Exocytosis
  • Endocytosis
  • Glycolysis

Correct Answer: Autophagy

Q15. Which ribosomal protein mutation is most likely to impair ribosome assembly and cause cell injury?

  • Mutant RPL5
  • Mutant actin
  • Mutant tubulin
  • Mutant cyclin D

Correct Answer: Mutant RPL5

Q16. Which cellular structure is the primary site of ribosome assembly?

  • Endoplasmic reticulum
  • Nucleolus
  • Golgi apparatus
  • Centrosome

Correct Answer: Nucleolus

Q17. Which molecular event is an early indicator of translational stress?

  • eIF2α dephosphorylation
  • eIF2α phosphorylation
  • Increased polysome formation
  • Enhanced proteasome activity

Correct Answer: eIF2α phosphorylation

Q18. Drug-induced inhibition of mitochondrial ribosomes most directly impairs:

  • Nuclear transcription
  • Mitochondrial protein synthesis and ATP production
  • Lysosomal acidification
  • Plasma membrane integrity

Correct Answer: Mitochondrial protein synthesis and ATP production

Q19. Which protein is a sensor that detects ribosomal collision and initiates a stress response?

  • Gcn2
  • mTOR
  • Akt
  • Ras

Correct Answer: Gcn2

Q20. Ribosomal stalling during translation elongation can trigger formation of:

  • Stress granules
  • Peroxisomes
  • Golgi stacks
  • Desmosomes

Correct Answer: Stress granules

Q21. Which class of drugs is most associated with causing ribosomal damage in bacteria by inhibiting peptidyl transferase?

  • Macrolides
  • Fluoroquinolones
  • Beta-lactams
  • Sulfonamides

Correct Answer: Macrolides

Q22. Chronic impairment of protein synthesis can lead to organ dysfunction by reducing:

  • Cellular adhesion molecules
  • Repair and regenerative protein pools
  • Extracellular calcium
  • Lipid bilayer fluidity

Correct Answer: Repair and regenerative protein pools

Q23. Which molecular marker indicates activation of the integrated stress response due to ribosomal stress?

  • LC3-II accumulation
  • Phospho-eIF2α increase
  • Decreased caspase activity
  • Increased ATP levels

Correct Answer: Phospho-eIF2α increase

Q24. Proteotoxic stress from ribosome damage commonly activates which transcription factor to increase chaperone expression?

  • HIF-1α
  • ATF6
  • NF-κB
  • c-Myc

Correct Answer: ATF6

Q25. Which technique can directly visualize ribosomal RNA cleavage by ribotoxins?

  • Northern blotting
  • Flow cytometry
  • Western blotting
  • Mass spectrometry of lipids

Correct Answer: Northern blotting

Q26. Excessive activation of UPR due to prolonged ribosomal dysfunction often results in:

  • Cell survival and proliferation
  • Apoptosis
  • Immediate cell cycle entry
  • Enhanced mitochondrial biogenesis

Correct Answer: Apoptosis

Q27. Which ribosomal-targeting event is characteristic of aminoglycoside toxicity in eukaryotic cells?

  • Inhibition of 60S assembly only
  • Mitochondrial ribosome interference leading to ototoxicity
  • Complete protection of mitochondrial translation
  • Activation of DNA polymerase

Correct Answer: Mitochondrial ribosome interference leading to ototoxicity

Q28. Which cellular degradation system removes individual misfolded proteins before autophagy is engaged?

  • Lysosomal exocytosis
  • Ubiquitin-proteasome system
  • Ribosomal recycling
  • Endoplasmic reticulum export

Correct Answer: Ubiquitin-proteasome system

Q29. Inhibition of ribosomal function during ischemia-reperfusion injury mainly contributes to cell damage by:

  • Reducing antioxidant enzyme synthesis
  • Increasing glycogen stores
  • Stabilizing membranes
  • Enhancing ATP production

Correct Answer: Reducing antioxidant enzyme synthesis

Q30. Which small nucleolar RNAs (snoRNAs) are important for rRNA processing and proper ribosome function?

  • miR-21 family
  • C/D box and H/ACA box snoRNAs
  • tRNA-derived fragments
  • siRNAs targeting mRNA

Correct Answer: C/D box and H/ACA box snoRNAs

Q31. Ribosomal protein haploinsufficiency can cause developmental disorders termed:

  • Ribosomopathies
  • Mitochondriopathies
  • Glycoproteinoses
  • Lysosomal storage diseases

Correct Answer: Ribosomopathies

Q32. Which event best explains how ribosome damage may activate p53-mediated apoptosis?

  • Release of ribosomal proteins that bind MDM2
  • Direct phosphorylation of p53 by ribosomes
  • Sequestration of p53 in the ER
  • Increased translation of MDM2

Correct Answer: Release of ribosomal proteins that bind MDM2

Q33. Which cellular marker would most likely increase during ribosomal stress and autophagy activation?

  • p62/SQSTM1 accumulation
  • LC3-II level increase
  • Decrease in Beclin-1
  • ATP surge

Correct Answer: LC3-II level increase

Q34. Which ribosome-associated quality control (RQC) process rescues stalled nascent polypeptides?

  • Ribosome recycling by ABCE1
  • Ubiquitination and proteasomal degradation of nascent chains
  • mRNA splicing enhancement
  • Lipidation of ribosomes

Correct Answer: Ubiquitination and proteasomal degradation of nascent chains

Q35. Which compound is a classic inhibitor of mitochondrial protein synthesis and can cause bone marrow suppression?

  • Chloramphenicol
  • Tetracycline
  • Penicillin
  • Vancomycin

Correct Answer: Chloramphenicol

Q36. Ribosomal RNA methylation defects primarily affect:

  • Membrane potential
  • Ribosome assembly and function
  • DNA methylation patterns
  • Glycolytic flux

Correct Answer: Ribosome assembly and function

Q37. Which signaling kinase is activated by amino acid deprivation and ribosomal stress to reduce translation?

  • mTORC1
  • GCN2
  • ERK1/2
  • PKA

Correct Answer: GCN2

Q38. An increase in free 40S or 60S ribosomal subunits with decreased polysomes suggests:

  • Enhanced translation initiation
  • Translational inhibition or elongation block
  • Increased secretory protein output
  • Hyperactive ribosome biogenesis

Correct Answer: Translational inhibition or elongation block

Q39. Which therapeutic strategy could protect cells from ribosomal stress-induced apoptosis?

  • PERK pathway inhibitors that reduce CHOP induction
  • Agents that increase DNA mutation rates
  • Proteasome inhibitors to block degradation
  • Ribotoxin administration

Correct Answer: PERK pathway inhibitors that reduce CHOP induction

Q40. Which ribosomal phenomenon is likely responsible for synthesis of truncated polypeptides under ribosomal cleavage?

  • Premature translation termination
  • Enhanced readthrough of stop codons
  • Increased ribosome recycling efficiency
  • Co-translational folding acceleration

Correct Answer: Premature translation termination

Q41. Which cellular compartment contains membrane-bound ribosomes involved in secretory protein synthesis?

  • Rough endoplasmic reticulum
  • Mitochondrial matrix
  • Cytosol free ribosomes only
  • Peroxisomal lumen

Correct Answer: Rough endoplasmic reticulum

Q42. Ribosomal protein S6 phosphorylation is commonly used as a readout for activation of which pathway?

  • mTOR signaling
  • UPR PERK branch
  • p53 tumor suppressor pathway
  • Autophagy initiation only

Correct Answer: mTOR signaling

Q43. Which laboratory marker would indicate impaired ribosome biogenesis in the nucleolus?

  • Reduced levels of pre-rRNA transcripts
  • Increased 18S rRNA levels only
  • Elevated cytosolic calcium
  • Increased glycogen content

Correct Answer: Reduced levels of pre-rRNA transcripts

Q44. Which event links ribosomal stress to systemic inflammation in severe toxicity?

  • Release of damage-associated molecular patterns (DAMPs)
  • Immediate restoration of translation
  • Decreased cytokine production
  • Suppression of NF-κB

Correct Answer: Release of damage-associated molecular patterns (DAMPs)

Q45. Which drug class can cause mitochondrial ribosomal toxicity leading to lactic acidosis?

  • Nucleoside reverse transcriptase inhibitors (NRTIs)
  • Nonsteroidal antiinflammatories
  • Beta-blockers
  • ACE inhibitors

Correct Answer: Nucleoside reverse transcriptase inhibitors (NRTIs)

Q46. Ribosomal stress can lead to selective translation of specific mRNAs such as ATF4 via:

  • Upstream open reading frames (uORFs) regulation
  • Alternative splicing of mRNA caps
  • Increased polyadenylation of all mRNAs
  • Direct ribosomal binding to promoters

Correct Answer: Upstream open reading frames (uORFs) regulation

Q47. Which cellular phenomenon describes failure to produce essential proteins causing irreversible cell injury?

  • Reversible cell swelling
  • Loss of functional homeostasis and irreversible injury
  • Adaptive hypertrophy
  • Physiologic hyperplasia

Correct Answer: Loss of functional homeostasis and irreversible injury

Q48. Which method helps detect ribosomal protein release from nucleolus to nucleoplasm during stress?

  • Immunofluorescence microscopy
  • Gas chromatography
  • Electrophoretic mobility shift assay for DNA
  • Lipid extraction

Correct Answer: Immunofluorescence microscopy

Q49. Which cellular consequence is least likely directly caused by ribosome damage?

  • Impaired secreted enzyme production
  • Defective membrane receptor synthesis
  • Immediate increase in DNA methylation globally
  • Altered stress-response protein levels

Correct Answer: Immediate increase in DNA methylation globally

Q50. Which preventive strategy is most relevant when designing drugs to avoid ribosome-mediated toxicity?

  • Assessing off-target effects on mitochondrial and cytosolic ribosomes
  • Maximizing lipophilicity irrespective of selectivity
  • Inhibiting all protein synthesis broadly
  • Avoiding any preclinical safety testing

Correct Answer: Assessing off-target effects on mitochondrial and cytosolic ribosomes

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