The pathogenesis of cell injury – mitochondrial damage is a central topic for B. Pharm students studying how drugs and toxins disrupt cellular energy metabolism. Mitochondrial damage leads to ATP depletion, increased reactive oxygen species (ROS), loss of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore (mPTP), triggering apoptosis or necrosis. Understanding mechanisms such as cytochrome c release, cardiolipin oxidation, calcium overload, and mtDNA injury helps predict drug-induced toxicity and design protective therapies. This focused review emphasizes molecular events, diagnostic assays, and pharmacological modulators relevant to pharmaceutical practice. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which event is most directly responsible for initiating intrinsic apoptosis in mitochondrial damage?
- Activation of death receptors on the cell surface
- Excessive ATP production by mitochondria
- Release of cytochrome c into the cytosol
- Increased lysosomal enzyme activity
Correct Answer: Release of cytochrome c into the cytosol
Q2. Opening of the mitochondrial permeability transition pore (mPTP) typically results in:
- Enhanced oxidative phosphorylation and ATP synthesis
- Mitochondrial swelling and loss of membrane potential
- Reduced reactive oxygen species (ROS) production
- Stabilization of mitochondrial DNA
Correct Answer: Mitochondrial swelling and loss of membrane potential
Q3. Which ETC complex is the primary site of superoxide generation when inhibited?
- Complex IV (cytochrome c oxidase)
- Complex III (ubiquinol-cytochrome c reductase)
- Complex II (succinate dehydrogenase)
- ATP synthase (Complex V)
Correct Answer: Complex III (ubiquinol-cytochrome c reductase)
Q4. Which of the following is a common indicator of severe mitochondrial injury in cells?
- Increased glycolytic flux with normal ATP levels
- Decreased cytosolic calcium concentration
- ATP depletion and loss of membrane potential
- Elevated mitochondrial biogenesis markers
Correct Answer: ATP depletion and loss of membrane potential
Q5. Cardiolipin oxidation in the inner mitochondrial membrane promotes:
- Stabilization of ETC complexes
- Anchoring of cytochrome c to the inner membrane
- Detachment and release of cytochrome c
- Enhanced ATP synthase activity
Correct Answer: Detachment and release of cytochrome c
Q6. Which ion overload is most closely associated with opening of mPTP during cell injury?
- Sodium overload
- Potassium overload
- Calcium overload
- Chloride overload
Correct Answer: Calcium overload
Q7. Which drug class acts as mitochondrial uncouplers by dissipating proton gradient?
- Proton pump inhibitors
- Uncoupling agents like FCCP and 2,4-dinitrophenol
- Complex I inhibitors like rotenone
- ATP synthase activators
Correct Answer: Uncoupling agents like FCCP and 2,4-dinitrophenol
Q8. Rotenone toxicity primarily inhibits which mitochondrial component?
- Complex IV
- Complex I
- Complex II
- ATP synthase
Correct Answer: Complex I
Q9. Which measurement is most direct for assessing mitochondrial membrane potential in living cells?
- Western blot for cytochrome c
- JC-1 or TMRM fluorescent dye assays
- Measurement of lactate dehydrogenase release
- mRNA expression of PGC-1α
Correct Answer: JC-1 or TMRM fluorescent dye assays
Q10. Which reactive species is formed by reaction of nitric oxide with superoxide in mitochondria?
- Hydrogen peroxide
- Peroxynitrite
- Hydroxyl radical
- Singlet oxygen
Correct Answer: Peroxynitrite
Q11. Loss of mitochondrial DNA integrity primarily affects cells by impairing:
- Glycolysis enzymes
- Transcription in the nucleus
- Electron transport chain protein synthesis
- Lysosomal enzyme activity
Correct Answer: Electron transport chain protein synthesis
Q12. Which protein family regulates mitochondrial outer membrane permeabilization (MOMP)?
- Caspase family
- Bcl-2 family
- Toll-like receptors
- Cytochrome P450 enzymes
Correct Answer: Bcl-2 family
Q13. Cytochrome c release from mitochondria activates which downstream pathway?
- MAP kinase survival pathway
- Intrinsic apoptotic cascade via caspase-9
- Extracellular matrix remodeling
- Protein kinase A signaling
Correct Answer: Intrinsic apoptotic cascade via caspase-9
Q14. Which assay is commonly used to quantify cellular ATP levels as an index of mitochondrial function?
- MTT assay measuring NADPH
- Lactate assay
- Luciferase-based ATP bioluminescence assay
- ELISA for cytochrome c
Correct Answer: Luciferase-based ATP bioluminescence assay
Q15. During ischemia-reperfusion injury, the initial surge in mitochondrial ROS occurs mainly at reperfusion because:
- Mitochondria increase ATP production suddenly
- Electron transport chain becomes fully reduced and oxygen returns
- mPTP permanently closes
- Calcium efflux from mitochondria is increased
Correct Answer: Electron transport chain becomes fully reduced and oxygen returns
Q16. Which molecule is a mitochondrial-specific antioxidant used experimentally to reduce oxidative damage?
- Vitamin C
- MitoQ
- Glucose
- Atorvastatin
Correct Answer: MitoQ
Q17. Which caspase is directly activated by the apoptosome after cytochrome c release?
- Caspase-3
- Caspase-8
- Caspase-9
- Caspase-1
Correct Answer: Caspase-9
Q18. Which change distinguishes necrosis from apoptosis in the context of mitochondrial damage?
- ATP-dependent chromatin condensation in necrosis
- Fade of membrane integrity and inflammatory response in necrosis
- Programmed cell corpse formation in necrosis
- Selective caspase activation in necrosis
Correct Answer: Fade of membrane integrity and inflammatory response in necrosis
Q19. Which drug is a known inhibitor of ATP synthase (Complex V)?
- Oligomycin
- Cyanide
- Rotenone
- Antimycin A
Correct Answer: Oligomycin
Q20. Mitochondrial biogenesis is regulated by which transcriptional coactivator important in metabolic adaptation?
- NF-κB
- PGC-1α
- AP-1
- CREB
Correct Answer: PGC-1α
Q21. In drug-induced mitochondrial toxicity screening, which parameter is least informative?
- Oxygen consumption rate (OCR)
- ATP content
- Δψm measurement
- Serum cholesterol level
Correct Answer: Serum cholesterol level
Q22. Mitophagy, the selective removal of damaged mitochondria, is mediated by which pathway involving Parkin?
- mTOR activation pathway
- PINK1/Parkin ubiquitination pathway
- NFAT signaling
- cAMP-PKA pathway
Correct Answer: PINK1/Parkin ubiquitination pathway
Q23. Which lipid located in the inner mitochondrial membrane is essential for optimal function of several ETC complexes?
- Phosphatidylserine
- Cardiolipin
- Sphingomyelin
- Cholesterol
Correct Answer: Cardiolipin
Q24. Permeabilization of the outer mitochondrial membrane allows release of which pro-apoptotic factor besides cytochrome c?
- Bcl-2
- SMAC/DIABLO
- ATP synthase
- Complex I subunits
Correct Answer: SMAC/DIABLO
Q25. Chronic accumulation of mitochondrial DNA mutations in tissues primarily leads to:
- Acute inflammatory responses only
- Progressive bioenergetic failure and disease
- Immediate necrotic cell death
- Enhanced mitochondrial fusion exclusively
Correct Answer: Progressive bioenergetic failure and disease
Q26. Which reagent is classically used experimentally to inhibit Complex IV of the ETC?
- Antimycin A
- Cyanide
- FCCP
- Oligomycin
Correct Answer: Cyanide
Q27. Which process helps maintain mitochondrial quality by fusing healthy and damaged mitochondria?
- Mitochondrial fission
- Mitochondrial fusion
- Autolysis
- Endocytosis
Correct Answer: Mitochondrial fusion
Q28. A decrease in mitochondrial membrane potential (Δψm) typically reduces which function?
- Glycolytic flux
- ATP synthesis by ATP synthase
- Protein synthesis in the cytosol
- DNA replication in the nucleus
Correct Answer: ATP synthesis by ATP synthase
Q29. Which of the following is a hallmark biochemical event of irreversible cell injury due to mitochondrial failure?
- Reversible chromatin clumping
- Persistent ATP depletion and plasma membrane rupture
- Transient loss of calcium homeostasis that is fully recovered
- Increased mitophagy restoring function
Correct Answer: Persistent ATP depletion and plasma membrane rupture
Q30. Which commonly used hepatotoxin produces mitochondrial damage as a key mechanism of liver injury?
- Paracetamol (acetaminophen)
- Ibuprofen at therapeutic doses
- Penicillin
- Metformin at normal doses
Correct Answer: Paracetamol (acetaminophen)
Q31. In the context of mitochondrial ROS production, which enzyme detoxifies hydrogen peroxide to water?
- Superoxide dismutase (SOD)
- Glutathione peroxidase
- NADPH oxidase
- Tyrosine kinase
Correct Answer: Glutathione peroxidase
Q32. Which mitochondrial parameter measured by Seahorse analyzer indicates coupling efficiency between respiration and ATP production?
- Proton leak measurement
- Maximal glycolytic capacity
- Basal extracellular acidification rate
- Spare respiratory capacity
Correct Answer: Spare respiratory capacity
Q33. Which Bcl-2 family member is pro-apoptotic and promotes mitochondrial outer membrane permeabilization?
- Bcl-2
- Mcl-1
- Bax
- Bcl-xL
Correct Answer: Bax
Q34. Which mitochondrial change is primarily responsible for reduced capacity to buffer cytosolic calcium during injury?
- Increased mitochondrial mass
- Loss of membrane potential
- Enhanced ATP synthesis
- Overexpression of PGC-1α
Correct Answer: Loss of membrane potential
Q35. Which assay best distinguishes early apoptotic cells from necrotic cells by detecting phosphatidylserine exposure?
- Annexin V binding assay
- Comet assay
- ATP luminescence assay
- Mitochondrial DNA sequencing
Correct Answer: Annexin V binding assay
Q36. Mitochondrial swelling during severe injury is due to:
- Increased protein synthesis inside mitochondria
- Influx of solutes and water following mPTP opening
- Active export of calcium ions
- Enhanced cristae formation
Correct Answer: Influx of solutes and water following mPTP opening
Q37. Which small molecule can inhibit mPTP opening and protect mitochondria experimentally?
- Cyclosporin A
- Rotenone
- Antimycin A
- FCCP
Correct Answer: Cyclosporin A
Q38. Loss of which mitochondrial function shifts cells toward anaerobic metabolism and lactate production?
- Oxidative phosphorylation
- Gluconeogenesis
- Lipid synthesis
- Urea cycle
Correct Answer: Oxidative phosphorylation
Q39. Which mitochondrial enzyme converts superoxide to hydrogen peroxide?
- Catalase
- Superoxide dismutase (SOD)
- Glutathione reductase
- Peroxiredoxin
Correct Answer: Superoxide dismutase (SOD)
Q40. Which pathology is most classically associated with primary mitochondrial DNA mutations?
- Osteoarthritis
- Leber’s hereditary optic neuropathy
- Rheumatoid arthritis
- Type I hypersensitivity
Correct Answer: Leber’s hereditary optic neuropathy
Q41. Which statement about mitochondrial involvement in drug toxicity is correct?
- All drugs that impair mitochondria cause immediate apoptosis only
- Mitochondrial dysfunction can lead to both necrosis and apoptosis depending on ATP levels
- Mitochondrial damage is irrelevant to organ-specific toxicity
- Drugs never affect mitochondrial DNA
Correct Answer: Mitochondrial dysfunction can lead to both necrosis and apoptosis depending on ATP levels
Q42. Which mitochondrial parameter increases during oxidative phosphorylation uncoupling?
- ATP production efficiency
- Oxygen consumption without ATP synthesis
- Δψm becomes hyperpolarized
- Electron transport stops completely
Correct Answer: Oxygen consumption without ATP synthesis
Q43. The presence of which cytosolic complex indicates formation of the apoptosome?
- Apaf-1 complexed with cytochrome c and procaspase-9
- mTORC1 activation complex
- Proteasome 26S assembly
- Inflammasome activating caspase-1
Correct Answer: Apaf-1 complexed with cytochrome c and procaspase-9
Q44. Which cellular adaptation increases mitochondrial number in response to endurance training or metabolic demand?
- Mitochondrial fission due to Drp1 activation
- Mitochondrial biogenesis via PGC-1α activation
- Immediate mitophagy of all mitochondria
- Suppression of oxidative phosphorylation permanently
Correct Answer: Mitochondrial biogenesis via PGC-1α activation
Q45. Which laboratory marker reflects necrotic cell death secondary to mitochondrial failure in tissue?
- No change in extracellular enzymes
- Increased release of intracellular enzymes like LDH
- Decreased serum transaminases despite injury
- Selective increase in mitochondrial DNA in the nucleus
Correct Answer: Increased release of intracellular enzymes like LDH
Q46. Which therapeutic strategy targets mitochondrial ROS to protect against drug-induced injury?
- Inhibition of glycolysis exclusively
- Administration of mitochondria-targeted antioxidants like MitoQ
- Blocking autophagy globally
- Enhancing peroxynitrite formation
Correct Answer: Administration of mitochondria-targeted antioxidants like MitoQ
Q47. Which change is expected in cells with defective complex I activity?
- Reduced NADH oxidation and increased ROS
- Enhanced oxidation of succinate at complex II only
- Increased ATP production via oxidative phosphorylation
- Complete resistance to calcium overload
Correct Answer: Reduced NADH oxidation and increased ROS
Q48. Which hallmark indicates early mitochondrial-mediated apoptosis rather than late necrosis?
- Plasma membrane rupture and inflammation
- Early externalization of phosphatidylserine with intact membrane
- Massive ATP loss before any caspase activation
- Complete mitochondrial DNA degradation only
Correct Answer: Early externalization of phosphatidylserine with intact membrane
Q49. Which experimental intervention would most likely increase mitophagy of damaged mitochondria?
- Inhibition of PINK1 accumulation on damaged mitochondria
- Activation of Parkin-mediated ubiquitination
- Overexpression of anti-apoptotic Bcl-2 only
- Blocking lysosomal function completely
Correct Answer: Activation of Parkin-mediated ubiquitination
Q50. In designing safer drugs, which mitochondrial parameter should be routinely evaluated during preclinical screening?
- Ability to increase plasma glucose only
- Effects on oxygen consumption, ATP levels, and Δψm
- Changes in melanin synthesis
- Alteration of hair follicle cycling
Correct Answer: Effects on oxygen consumption, ATP levels, and Δψm
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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