Mitochondrial Intoxication

Front Cover
Mitochondrial Intoxication
Copyright
Dedication
Contents
Contributors
Preface
Acknowledgments
Chapter 1: Mitochondrial physiology: An overview
1. Introduction
2. TCA cycle and oxidative phosphorylation system activity
3. Mitochondrial dynamics: Fusion and fission
3.1. Mitochondrial fusion
3.2. Mitochondrial fission
4. Mitochondrial biogenesis and mitophagy
4.1. Regulation of mitochondrial biogenesis
4.2. Mitophagy: Molecular mechanisms
4.3. Mitochondrial homeostasis: Coordination of mitochondrial biogenesis and mitophagy
4.4. Physiological functions of biogenesis and mitophagy
5. Mitochondria-related cell death
5.1. Mitochondrial role in apoptosis
5.2. Mitochondria in pyroptosis, necroptosis, and ferroptosis
6. Mitochondrial redox biology
6.1. Superoxide dismutase
6.2. Mitochondrial catalase and oxidative injury
6.3. Mitochondrial NADPH and redox homeostasis
6.4. Mitochondrial glutathione
7. Concluding remarks
References
Chapter 2: Molecular markers of mitochondrial intoxication
1. Mechanisms of interaction leading to mitochondrial injury
2. Markers of mitochondrial damage
2.1. ROS/RNS production by mitochondria
2.2. Protein nitration
2.3. Protein carbonylation
2.4. Lipid peroxidation
2.5. MMP loss
2.6. Opening of the MPT and apoptosis
2.7. Calcium metabolism dyshomeostasis
2.8. Damage to mitochondrial DNA
2.9. Bioenergetics failure
3. Chemical-induced mitochondrial damage: Case examples
3.1. Interference in membrane structure and functions
3.2. Inhibition and uncoupling of oxidative phosphorylation
3.3. Alteration of the calcium homeostasis
3.4. Complexation with biomolecules
4. Conclusions
References
Chapter 3: Drug-induced mitochondrial impairment: Mechanisms and testing systems
1. Introduction
2. Mechanisms of drug-induced mitochondrial impairment
2.1. Changes in mitochondrial membrane composition and integrity
2.2. The inhibition of mitochondrial respiratory chain components
2.3. Mitochondrial permeabilization
2.4. Mitochondrial DNA damage
2.5. Effects of drugs on the uptake of molecules required for mitochondrial function
2.6. Drugs with protonophoretic and oxidative phosphorylation uncoupling activity
3. Testing systems for evaluating drug-induced mitochondrial impairment
4. Biomarkers of drug-induced mitochondrial injury in clinical settings
5. Protective strategies against drug-induced mitochondrial dysfunction
6. Outlook
Conflicts of interest
References
Chapter 4: Clinical consequences of drug-induced mitochondrial dysfunction
Abbreviations
1. Introduction
2. Clinical manifestations of drug-induced mitochondrial dysfunction
2.1. Hepatotoxicity
2.1.1. Steatosis
2.1.1.1. Mitochondrial involvement
2.1.1.2. Clinical examples
2.1.2. Acute liver failure
2.1.2.1. Mitochondrial involvement
2.1.2.2. Clinical examples
2.2. Skeletal muscle toxicity
2.2.1. Mitochondrial involvement
2.2.2. Clinical examples
2.3. Cardiotoxicity
2.3.1. Mitochondrial involvement
2.3.2. Clinical examples
2.4. Neuropathy
2.4.1. Mitochondrial involvement
2.4.2. Clinical examples
2.5. Nephrotoxicity
2.5.1. Mitochondrial involvement
2.5.2. Clinical examples
2.6. Ototoxicity
2.6.1. Mitochondrial involvement
2.6.2. Clinical examples
3. Interindividual variation
4. Concluding remarks
References
Chapter 5: Challenges in mitochondrial profiling during pre-clinical studies
Abbreviations and formulae
1. Introduction
1.1. Introduction to mitochondrial toxicology
1.2. Main roles of mitochondria
1.3. Examples of mitochondrial toxicity
2. Experimental models and conditions
3. Mitochondrial microscopy, concerns and pitfalls
3.1. Mitochondria under the microscope-Chemical dyes vs genetically encoded sensors
3.2. Caveats in mitochondrial microscopy studies
4. Studying mitochondrial biology using machine learning methodologies
4.1. Machine learning, friend or foe?
4.2. Machine learning approaches crucial role in mitochondrial biology and toxicology
5. Conclusion
Acknowledgments
References
Chapter 6: Mitochondrial dysfunction and underlying molecular mechanisms in acrylamide-induced toxicity
1. Introduction
2. AA induces the destruction and dysfunction of mitochondria
3. AA induces DNA damage and influences cell cycle and growth
4. AA induces extensive oxidative stress in mitochondria
5. Signaling pathways involved in mitochondrial dysfunction induced by AA
5.1. Collapse of antioxidant system's nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway
5.2. AA could damage mitochondria via mitogen-activated protein kinase (MAPK) signaling pathway
5.3. AA regulates nuclear factor (NF)-κB signaling pathway to initiate inflammation and damage mitochondria
5.4. AA could damage mitochondria via PI3K/AKT/mTOR signaling pathway
6. Conclusion
References
Chapter 7: The effects of air pollution toxicants on the mitochondria
1. Introduction
2. Mitochondria structure and function
3. Mitochondrial dynamics
4. Oxidative stress and the mitochondria
5. Major types of hazardous air pollutants
6. Major organs affected by air pollutants and disease exacerbations
7. Air pollutants as a source of ROS in the mitochondria
8. Conclusion
9. Future direction
Acknowledgments
References
Chapter 8: Mitochondrial toxicity of aflatoxin B1
1. Introduction
2. Biotransformation of AFB1
3. AFB1 toxicity of the mitochondria
3.1. AFB1 toxicity in the mitochondria: Lipids
3.2. AFB1 toxicity in the mitochondria: Membrane potential and permeability
3.3. AFB1 toxicity in the mitochondria: Oxidative stress and apoptosis
3.4. AFB1 toxicity in the mitochondria: Respiratory chain enzymes
4. Conclusion
References
Chapter 9: The effects of alcohol abuse against the mitochondria: Functional consequences for liver, muscle, and the brain
1. Introduction
2. Alcohol toxicity
2.1. Alcohol consumption in our current society
2.2. Types of alcohol consumption
3. Alcohol consumption affects mitochondrial function
3.1. Alcohol impairs mitochondria in the liver
3.2. Alcohol impairs mitochondrial health in muscle cells
3.3. Association of alcohol consumption with brain abnormalities
4. Strategies to reduce mitochondrial injury induced by alcohol
4.1. Enhancing mitochondrial function to reduce alcohol-induced liver disease
4.2. Reversing mitochondria injury to reduce muscle disease induced by alcohol
4.3. Activation of melanocortin system and Nrf2 antioxidant pathway to reduce brain mitochondrial dysfunction induced by ...
5. Conclusions
Acknowledgments
References
Further reading
Chapter 10: The effect of aluminum on mitochondrial dysfunctions
1. Introduction
2. Aluminum and human exposure
3. Aluminum toxicokinetic
4. Basic mechanism of action of aluminum
5. Mitochondrion as a target organelle for Al toxicity
5.1. Production of aluminum-superoxide anion complexes in the mitochondrial matrix
5.2. Oxidative environment leads to lipid peroxidation of mitochondrial membranes
5.3. Disturbance in the activity of antioxidant enzymes after aluminum exposure
5.4. Disruption of mitochondrial energy metabolism mediated by aluminum
5.5. Effects of aluminum and the elevated concentrations of mitochondrial α-ketoglutarate
5.6. Aluminum exposure and oxidation of mtDNA
5.7. Aluminum toxicity and impairment of the mitochondrial quality control
6. Aluminum toxicity and the consequences to high energy-requiring tissues
6.1. Aluminum toxicity and mitochondrial dysfunction in neurological disorders
6.2. Hepatic damages and metabolic shift in lipogenesis after aluminum exposure
6.3. Cardiac tissue and mitochondrial dysfunction caused by aluminum
7. Conclusion
Acknowledgments
References
Chapter 11: Discovery of amiodarone mitochondrial toxicity in liver and beyond
1. Introduction
2. Amiodarone-induced hepatotoxicity
3. Drug-induced microvesicular steatosis and mitochondrial dysfunction
4. First evidence that amiodarone could inhibit mitochondrial FAO
5. Amiodarone-induced inhibition of the mitochondrial respiratory chain
6. Amiodarone-induced uncoupling of oxidative phosphorylation
7. Amiodarone accumulates within the mitochondria
8. Amiodarone-induced mitochondrial dysfunction: A schematic overview
9. Subsequent confirmation that amiodarone can impair mitochondrial functions
10. From mitochondrial dysfunction to hepatic steatosis and steatohepatitis
11. Amiodarone-induced mitochondrial dysfunction in other tissues
12. Concluding remarks
Acknowledgment
References
Chapter 12: Ammonia
1. Introduction: Ammonia metabolism, hyperammonemia, and hepatic encephalopathy
2. Mitochondria: The main subcellular target of ammonia toxicity
3. Effects of ammonia on organs other than CNS
4. Therapeutic approaches and future perspectives
Conflicts of interest
References
Chapter 13: Mitochondrial disruption as a contributing factor for the neurotoxicity of amphetamines
1. Introduction
2. The tricarboxylic acid cycle as a target of amphetamines
3. Effects of amphetamines on the mitochondrial electron transport chain
3.1. Changes in oxygen consumption and ATP levels as readout of altered functions of the mitochondrial electron transport ...
3.2. Changes in mitochondrial membrane potential as a readout of altered function of the mitochondrial electron transport ...
3.3. Increased formation of reactive oxygen species as readout of altered function of the mitochondrial electron transpor ...
4. Amphetamines and the outer mitochondrial membrane enzymes monoamine oxidase
5. Effects of amphetamines on the mitochondrial biogenesis
6. Effects of amphetamines on mitochondrial survival mechanisms
7. Amphetamines impair the mitochondrial fusion/fission equilibrium
8. Effects of amphetamines on the distribution and transport dynamics of mitochondria
9. Concluding remarks
References
Chapter 14: Mitochondrial intoxication by anthracyclines
1. Introduction
2. Cardiotoxicity
3. Skeletal muscle toxicity
4. Endothelial vascular toxicity
5. Liver toxicity
6. Nephrotoxicity
7. Neurotoxicity
8. Mitochondrial intoxication in cancer cells
9. Conclusion
References
Chapter 15: Antidepressants, mood-stabilizing drugs, and mitochondrial functions: For better or for worse
1. Introduction
2. Mitochondrial energy metabolism and psychopathology
3. How mitochondrial functions are assessed?
4. The effects of antidepressants and psychiatric drugs on mitochondrial functions
4.1. Selective serotonin reuptake inhibitors: Evidence from animal studies
4.2. Selective serotonin reuptake inhibitors: Evidence from human studies
4.3. Tricyclic antidepressants: Evidence from animal studies
4.4. Tricyclic antidepressants: Evidence from human studies
4.5. Serotonin-norepinephrine (SNRI) and norepinephrine-dopamine reuptake inhibitors (NDRI): Evidence from animal studies
4.6. Serotonin-norepinephrine (SNRI) and norepinephrine-dopamine reuptake inhibitors (NDRI): Evidence from human studies
4.7. Antipsychotics: Evidence from animal studies
4.8. Other antidepressant drugs: Evidence from animal studies
4.9. Other antidepressant drugs: Evidence from human studies
5. Discussion
6. Knowledge gaps
7. Conclusions
References
Chapter 16: The effects of HIV and the antiretrovirals on the mitochondria
1. Human immunodeficiency virus
1.1. HIV structure
1.2. Epidemiology
1.3. Viral life cycle
1.4. Clinical features
1.5. HIV and mitochondria
2. Mitochondrial damage measurements
3. Antiretroviral therapy
3.1. Drug indications for HIV in clinical practice
3.2. Drug families and associated secondary effects
3.2.1. Nucleoside transcriptase inhibitors (NRTIs)
3.2.2. Non-nucleoside transcriptase inhibitors (NNRTIs)
3.2.3. Protease inhibitors (PIs)
3.2.4. Integrase inhibitors or integrase strand transfer inhibitors (INSTIs)
3.2.5. Fusion inhibitors (FIs)
3.2.6. Entry inhibitors (CCR5 inhibitors)
4. Discussion
References
Chapter 17: The effect of arsenical compounds on mitochondrial metabolism
1. Introduction
2. Physicochemical properties of arsenic and arsenical compounds
3. Arsenic poisoning and the risk for human health
4. Intracellular metabolism of pentavalent and trivalent arsenicals
4.1. Arsenate reduction to arsenite
4.2. Arsenite biomethylation
5. Toxic mechanism of arsenical compounds
6. Mitochondria as target organelles to arsenic toxicity
6.1. Disruption of the tricarboxylic acid cycle and ATP production mediated by trivalent arsenicals
6.2. ROS overproduction in the mitochondrial electron transport chain mediated by trivalent arsenicals
6.3. Mitochondrial antioxidant system disruption by trivalent arsenicals
6.4. Mitochondrial oxidative damages and alteration on membrane potential induced by trivalent arsenicals
6.5. Trivalent arsenic effects on mitochondrial dynamics
6.6. Trivalent arsenic effects on calcium homeostasis and apoptosis
7. Amelioration of arsenic-induced mitochondrial oxidative stress and dysfunction
8. Conclusion
Acknowledgments
References
Chapter 18: Mechanisms of bisphenol A toxicity in mitochondria
1. Bisphenol A toxicity
2. Mitochondrial disease and BPA toxicity
3. Mitochondrial metabolism in BPA toxicity
4. Mitochondrial oxidative stress in BPA toxicity
5. Nrf2/Keap1 pathway and BPA toxicity
6. Mitochondrial respiration and the ROS-mediated mitochondrial pathway in BPA toxicity
7. Mitochondrial membrane potential and BPA toxicity
8. Mitochondria-mediated apoptosis pathway and BPA toxicity
9. Mitochondrial biogenesis in BPA toxicity
10. Mitophagy pathway in BPA toxicity
11. Mitochondrial dysfunction in BPA toxicity: Miscellaneous
12. Conclusion/future directions
References
Chapter 19: Chemotherapeutic drugs
1. Role of mitochondria in cancer
2. Targeting mitochondria for anticancer therapy
3. Mitochondria as the target for chemiotherapeutics side effects
3.1. Doxorubicin
3.2. Trastuzumab
3.3. Sunitinib
4. Conclusions
References
Chapter 20: Effects of cuprizone on mitochondria
1. Introduction to cuprizone
2. Cuprizone and mitochondrial dysfunction
2.1. Cuprizone and neuronal mitochondria and metabolism
2.2. Cuprizone and glial mitochondria and metabolism
2.3. Cuprizone and hepatic mitochondria
3. Advances in ameliorating mitochondrial damage from cuprizone
3.1. Betaine
3.2. Melatonin
3.3. Erythropoietin
4. Final remarks and conclusion
References
Further reading
Chapter 21: Effects of Delta9-tetrahydrocannabinol on mitochondria
1. Endocannabinoid system
1.1. Endocannabinoids and their endogenous targets
1.2. Physiological targets and receptors of phytocannabinoids
2. Role of mitochondria in endocannabinoid signaling
2.1. Effects of phytocannabinoids on mitochondrial functions
3. Mitochondrial functions and cellular health
3.1. Mitochondrial dynamics, biogenesis, and mitophagy
3.2. Mitochondrial dynamics and cellular differentiation
3.3. Implications of cannabinoid-induced mitochondrial dysfunction on cellular health
4. Conclusion
References
Chapter 22: Effects of food additives on the mitochondria integrity and functioning
1. Introduction
2. Effect of food additives on mitochondria studied by in vitro experimentation
3. Isolated mitochondria experimentation (ex vivo)
4. Food additives that alter the mitochondria-dependent apoptosis
5. Food additives affecting ROS production in mitochondria
6. Food additives affecting the electron transport chain and metabolism in mitochondria
7. Effect of food additives on mitochondria in vivo experimentation
8. Conclusion
References
Chapter 23: Mitochondria as a toxicological target for fungicides
1. The use and relevance of fungicides-A brief overview
1.1. Relevance for plant disease control
1.2. Relevance as therapeutic tools
1.3. Classification of the fungicides by mode of action-Relevance for fungicide resistance management
2. A mitochondria-driven journey through the eukaryotic kingdoms
2.1. Functional organization in fungi, plant, and animal cells-Similarities and differences
2.2. Mitochondria in cell metabolism networks
2.3. Mitochondria in cell signaling cascades
2.4. Mitochondria as a sensor of toxic agents that determine the fate of cell metabolism
3. Mitochondrial toxicity of fungicides-An organ-targeted analysis
3.1. Hepatotoxicity
3.2. Nephrotoxicity
3.3. Neurotoxicity
3.4. Reproductive toxicology
References
Chapter 24: The effects of methylglyoxal on the mitochondria
1. Introduction
2. Brief overview of methylglyoxal metabolism from mitochondrial standpoint
3. The direct effect of methylglyoxal on respiration
4. Indirect mitochondrial effects of methylglyoxal added in vivo or to cell cultures
4.1. Energy production and membrane potential
4.2. Mitochondrial morphology
4.3. Glycation of mitochondrial proteins
4.4. Influence of methylglyoxal on mitochondrial channels
4.5. ROS formation, antioxidant defense, and lipid peroxidation
4.6. Mitochondrion-dependent apoptosis
5. Conclusions and perspectives
References
Chapter 25: The effect of mercury on the mitochondria
1. Mercury
2. Mitochondria
3. Hg and mitochondria
4. Hg and sulfidryl (thiol/-SH) groups
5. Hg and glutathione
6. Hg and mitochondrial ETC
7. Hg and mitochondrial membrane potential
8. Hg and apoptosis
References
Chapter 26: Organohalides
Abbreviations
1. Introduction to organohalides
2. Mitochondria as targets to environmental contaminants
3. Organochlorine pesticides
3.1. Structure and industrial application
3.2. Organochlorine pesticides as environmental contaminants
3.3. Organochlorine pesticides as mitochondrial toxicants: In vitro evidence
3.4. Organochlorine pesticides as mitochondrial toxicants: In vivo evidence
3.4.1. Evidence from mammalian studies
3.4.2. Evidence from other non-mammalian models
3.5. Computational toxicology for elucidating mitochondrial targets of organochlorine pesticides: A case study with metho ...
4. Perfluorinated chemicals
4.1. Structure and industrial application
4.2. Perfluorinated chemicals as environmental contaminants
4.3. Perfluorinated chemicals as mitochondrial toxicants: In vitro evidence
4.4. Perfluorinated chemicals as mitochondrial toxicants: In vivo evidence
4.4.1. Evidence from mammalian studies
4.4.2. Evidence from other non-mammalian models
5. High throughput assessment of OHs as mitochondrial toxicants
6. Final conclusions
References
Chapter 27: The effects of organophosphate pesticides on mitochondria
1. Background
2. General characteristics of OPs
3. Mitochondrial dysfunction in OPs-induced neurotoxicity
4. Mitochondrial dysfunction in OPs-induced cardiotoxicity
5. Mitochondrial dysfunction in OPs-induced liver toxicity
6. Mitochondrial dysfunction in OPs-induced kidney toxicity
7. Mitochondrial dysfunction in OPs-induced immune toxicity
8. Mitochondrial dysfunction in OPs-induced toxicity in cancer cell
9. Mitochondrial dysfunction in OPs-induced muscular toxicity
10. Mitochondrial dysfunction in OPs-induced reproductive toxicity
11. Mitochondrial dysfunction in OPs-induced skin toxicity
12. Conclusion
References
Further reading
Chapter 28: Mitochondrial oxygen toxicity
1. Introduction
2. Mitochondria as sources and targets of oxygen toxicity
3. Therapeutic targeting of mitochondrial ROS against oxygen toxicity
4. Conclusions
References
Chapter 29: Polychlorinated biphenyls
1. Polychlorinated biphenyls
2. Structural requirements
3. Effects of PCBs on mitochondrial structure: Cristae and membrane integrity
4. Effects of PCBs on the electron transport chain and oxidative phosphorylation
5. Effects of PCBs on mitochondria-related oxidative stress and mitochondrial uncoupling
6. Effects of PCBs on calcium storage and apoptosis
7. Concluding remarks
Acknowledgments
References
Chapter 30: The effects of polycyclic aromatic hydrocarbons on mitochondria
1. Polycyclic aromatic hydrocarbons and their bioactivation
2. Mitochondria as relevant targets of PAH exposure
3. Effects of PAHs on mitochondria
3.1. Oxidative stress and cellular antioxidant systems
3.2. Mitochondrial bioenergetics
3.3. Mitochondrial and nuclear DNA
3.4. Structural damage, mitophagy, and apoptosis
4. Summary
References
Further reading
Chapter 31: The effects of pyrethroids on the mitochondria
1. Introduction
2. Pyrethroids mode of action and toxicity
3. Pyrethroids can induce mitochondrial dysfunction
3.1. Mitochondrial metabolism
3.2. Mitochondrial structure
3.3. Mitochondrial Ca2+
3.4. Mitochondrial apoptosis
3.5. Mitochondria and behavior
4. Concluding remarks
References
Chapter 32: The effects of sodium nitrate on mitochondria
1. Sources of exposure to nitrates
2. Metabolism of nitrates and its cellular effects
3. Mitochondrial dysfunction and morphological changes during nitrate exposure
4. Conclusions
References
Chapter 33: Mitochondrial zinc toxicity
1. Introduction
2. Zinc transport
3. Concentrations of Zn2+ in the cytosol and mitochondria
4. Zinc inhibition of mitochondrial bioenergetics
5. A role for Zn2+ in mitochondrial dynamics
6. Zinc concentrations in cell culture media
7. Conclusions
References
Index
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