Yvonne Will, PhD, is a Senior Director and the Head of Science and Technology Strategy, Drug Safety Research and Development at Pfizer, Connecticut, USA. In addition to the prior edition of this book, she co-edited Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers(Wiley, 2016).James A. Dykens, PhD, oversees EyeCyte Therapeutics, a start-up developing treatments for progressive blinding diseases via targeting mitochondrial dysfunction. He co-edited the first edition of this book.

• Volume 1List of Contributors xviiForeword xxixPart 1 Basic Concepts 11 Contributions of Plasma Protein Binding and Membrane Transporters to Drug]Induced Mitochondrial Toxicity 3Gavin P. McStay2 The Role of Transporters in Drug Accumulation and Mitochondrial Toxicity 15Kathleen M. Giacomini and Huan]Chieh Chien3 Structure–Activity Modeling of Mitochondrial Dysfunction 25Steve Enoch, Claire Mellor, and Mark Nelms4 Mitochondria]Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic Induced Toxicity 35Haider Raza, F. Peter Guengerich, and Narayan G. AvadhaniPart 2 Organ Drug Toxicity: Mitochondrial Etiology 475 Mitochondrial Dysfunction in Drug]Induced Liver Injury 49Annie Borgne]Sanchez and Bernard Fromenty6 Evaluating Mitotoxicity as Either a Single or Multi]Mechanistic Insult in the Context of Hepatotoxicity 73Amy L. Ball, Laleh Kamalian, Carol E. Jolly, and Amy E. Chadwick7 Cardiotoxicity of Drugs: Role of Mitochondria 93Zoltan V. Varga and Pal Pacher8 Skeletal Muscle Mitochondrial Toxicity 111Eric K. Herbert, Saul R. Herbert, and Karl E. Herbert9 Manifestations of Drug Toxicity on Mitochondria in the Nervous System 133Jochen H. M. Prehn and Irene Llorente]Folch10 Nephrotoxicity: Increasing Evidence for a Key Role of Mitochondrial Injury and Dysfunction and Therapeutic Implications 169Ana Belén Sanz, Maria Dolores Sanchez]Niño, Adrian M. Ramos, and Alberto Ortiz11 Mammalian Sperm Mitochondrial Function as Affected by Environmental Toxicants, Substances of Abuse, and Other Chemical Compounds 185Sandra Amaral, Renata S. Tavares, Sara Escada]Rebelo, Andreia F. Silva, and João Ramalho]SantosPart 3 Methods to Detect Mitochondrial Toxicity: In Vitro, Ex Vivo, In Vivo, Using Cells, Animal Tissues, and Alternative Models 20512 Biological and Computational Techniques to Identify Mitochondrial Toxicants 207Robert B. Cameron, Craig C. Beeson, and Rick G. Schnellmann13 The Parallel Testing of Isolated Rat Liver and Kidney Mitochondria Reveals a Calcium]Dependent Sensitivity to Diclofenac and Ibuprofen 217Sabine Schulz, Sabine Borchard, Tamara Rieder, Carola Eberhagen, Bastian Popper, Josef Lichtmannegger, Sabine Schmitt, and Hans Zischka14 In Vitro Methodologies to Investigate Drug]Induced Toxicities 229Rui F. Simões, Teresa Cunha]Oliveira, Cláudio F. Costa, Vilma A. Sardão, and Paulo J. Oliveira15 Combined Automated Measurement of Respiratory Chain Complexes and Oxidative Stress: A First Step to an Integrated View of Cell Bioenergetics 249Marc Conti, Thierry Delvienne, and Sylvain Loric16 Measurement of Mitochondrial Toxicity by Flow Cytometry 265Padma Kumar Narayanan and Nianyu Li17 MitoChip: A Transcriptomics Tool for Elucidation of Mechanisms of Mitochondrial Toxicity 275Varsha G. Desai, and G. Ronald Jenkins18 Using 3D Microtissues for Identifying Mitochondrial Liabilities 295Simon Messner, Olivier Frey, Katrin Rössger, Andy Neilson, and Jens M. Kelm19 Toward Mitochondrial Medicine: Challenges in Rodent Modeling of Human Mitochondrial Dysfunction 305David A. Dunn, Michael H. Irwin, Walter H. Moos, Kosta Steliou, and Carl A. Pinkert20 Measurement of Oxygen Metabolism In Vivo 315M. P. J. van Diemen, R. Ubbink, F. M. Münker, E. G. Mik, and G. J. Groeneveld21 Detection of Mitochondrial Toxicity Using Zebrafish 323Sherine S. L. Chan and Tucker Williamson22 MiRNA as Biomarkers of Mitochondrial Toxicity 347Terry R. Van Vleet and Prathap Kumar Mahalingaiah23 Biomarkers of Mitochondrial Injury After Acetaminophen Overdose: Glutamate Dehydrogenase and Beyond 373Benjamin L. Woolbright and Hartmut Jaeschke24 Acylcarnitines as Translational Biomarkers of Mitochondrial Dysfunction 383Richard D. Beger, Sudeepa Bhattacharyya, Pritmohinder S. Gill, and Laura P. James25 Mitochondrial DNA as a Potential Translational Biomarker of Mitochondrial Dysfunction in Drug]Induced Toxicity Studies 395Afshan N. Malik26 Predicting Off]Target Effects of Therapeutic Antiviral Ribonucleosides: Inhibition of Mitochondrial RNA Transcription 407Jamie J. Arnold and Craig E. Cameron27 Imaging of Mitochondrial Toxicity in the Kidney 419Andrew M. Hall, Joana R. Martins, and Claus D. Schuh28 Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability 429Anna]Liisa Nieminen, Venkat K. Ramshesh, and John J. Lemasters29 Quantifying Skeletal Muscle Mitochondrial Function In Vivo by 31P Magnetic Resonance Spectroscopy 443Graham J. Kemp  Volume 2List of Contributors xiiiForeword xxvPart 4 Reports from the Clinic 45730 Statin and Fibrate]Induced Dichotomy of Mitochondrial Function 459Viruna Neergheen, Alex Dyson, Luke Wainwright, and Iain P. Hargreaves31 Friend or Foe: Can Mitochondrial Toxins Lead to Similar Benefits as Exercise? 475Sofia Annis, Adeel Safdar, Eduardo Biala, Ayesha Saleem, Housaiyin Li, Priya Gandhi, Zoe Fleischmann, Carmen Castaneda]Sceppa, Jonathan L. Tilly, Dori C. Woods, and Konstantin Khrapko32 Involvement of Mitochondrial Dysfunction on the Toxic Effects Caused by Drugs of Abuse and Addiction 487Daniel José Barbosa, João Paulo Capela, Maria de Lourdes Bastos, and Félix Carvalho33 Drug]Induced Mitochondrial Toxicity during Pregnancy 509Diana Luz Juárez-Flores, Ana Sandra Hernández, Laura Garcia, Mariona Guitart]Mampel, Marc Catalan]Garcia, Ingrid Gonzalez]Casacuberta, Jose César Milisenda, Josep Maria Grau, Francesc Cardellach, Constanza Morén, and Glòria Garrabou34 Mitochondrial Toxicity in Children and Adolescents Exposed to Antiretroviral Therapy 521Antoni Noguera]Julian, Eneritz Velasco]Arnaiz, and Clàudia Fortuny35 Drug]Induced Mitochondrial Cardiomyopathy and Cardiovascular Risks in Children 529Neha Bansal, Mariana Gerschenson, Tracie L. Miller, Stephen E. Sallan, Jason Czachor, Hiedy Razoky, Ashley Hill, Miriam Mestre, and Steven E. Lipshultz36 Role of Mitochondrial Dysfunction in Linezolid]Induced Lactic Acidosis 547Alessandro Santini, Dario Ronchi, Daniela Piga, and Alessandro Protti37 Metformin and Lactic Acidosis 559Jean]Daniel Lalau38 Lessons Learned from a Phase I Clinical Trial of Mitochondrial Complex I Inhibition 563Cecilia C. Low Wang, Jeffrey L. Galinkin, and William R. Hiatt39 Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies 569Whitney S. Gibbs, Natalie E. Scholpa, Craig C. Beeson, and Rick G. Schnellmann40 Mitochondrial Toxicity Induced by Chemotherapeutic Drugs 593Luciana L. Ferreira, Ana Raquel Coelho, Paulo J. Oliveira, and Teresa Cunha]OliveiraPart 5 Environmental Toxicants and Mitochondria 61341 The Mitochondrial Exposome 615Douglas I. Walker, Kurt D. Pennell, and Dean P. Jones42 Central Mitochondrial Signaling Mechanisms in Response to Environmental Agents: Integrated Omics for Visualization 639Young]Mi Go, Karan Uppal, and Dean P. Jones43 Detection of Mitochondrial Toxicity of Environmental Pollutants Using Caenorhabditis elegans 655Laura L. Maurer, Anthony L. Luz, and Joel N. Meyer44 Persistent Organic Pollutants, Mitochondrial Dysfunction, and Metabolic Syndrome 691Hong Kyu Lee and Youngmi Kim Pak45 Cigarette Smoke and Mitochondrial Damage 709Jalal Pourahmad, Marjan Aghvami, Mohammad Hadi Zarei, and Parvaneh NaserzadehIndex 727

Yvonne Will, PhD, is a Senior Director and the Head of Science and Technology Strategy, Drug Safety Research and Development at Pfizer, Connecticut, USA. In addition to the prior edition of this book, she co-edited Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers(Wiley, 2016).James A. Dykens, PhD, oversees EyeCyte Therapeutics, a start-up developing treatments for progressive blinding diseases via targeting mitochondrial dysfunction. He co-edited the first edition of this book.

• Volume 1List of Contributors xviiForeword xxixPart 1 Basic Concepts 11 Contributions of Plasma Protein Binding and Membrane Transporters to Drug]Induced Mitochondrial Toxicity 3Gavin P. McStay2 The Role of Transporters in Drug Accumulation and Mitochondrial Toxicity 15Kathleen M. Giacomini and Huan]Chieh Chien3 Structure–Activity Modeling of Mitochondrial Dysfunction 25Steve Enoch, Claire Mellor, and Mark Nelms4 Mitochondria]Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic Induced Toxicity 35Haider Raza, F. Peter Guengerich, and Narayan G. AvadhaniPart 2 Organ Drug Toxicity: Mitochondrial Etiology 475 Mitochondrial Dysfunction in Drug]Induced Liver Injury 49Annie Borgne]Sanchez and Bernard Fromenty6 Evaluating Mitotoxicity as Either a Single or Multi]Mechanistic Insult in the Context of Hepatotoxicity 73Amy L. Ball, Laleh Kamalian, Carol E. Jolly, and Amy E. Chadwick7 Cardiotoxicity of Drugs: Role of Mitochondria 93Zoltan V. Varga and Pal Pacher8 Skeletal Muscle Mitochondrial Toxicity 111Eric K. Herbert, Saul R. Herbert, and Karl E. Herbert9 Manifestations of Drug Toxicity on Mitochondria in the Nervous System 133Jochen H. M. Prehn and Irene Llorente]Folch10 Nephrotoxicity: Increasing Evidence for a Key Role of Mitochondrial Injury and Dysfunction and Therapeutic Implications 169Ana Belén Sanz, Maria Dolores Sanchez]Niño, Adrian M. Ramos, and Alberto Ortiz11 Mammalian Sperm Mitochondrial Function as Affected by Environmental Toxicants, Substances of Abuse, and Other Chemical Compounds 185Sandra Amaral, Renata S. Tavares, Sara Escada]Rebelo, Andreia F. Silva, and João Ramalho]SantosPart 3 Methods to Detect Mitochondrial Toxicity: In Vitro, Ex Vivo, In Vivo, Using Cells, Animal Tissues, and Alternative Models 20512 Biological and Computational Techniques to Identify Mitochondrial Toxicants 207Robert B. Cameron, Craig C. Beeson, and Rick G. Schnellmann13 The Parallel Testing of Isolated Rat Liver and Kidney Mitochondria Reveals a Calcium]Dependent Sensitivity to Diclofenac and Ibuprofen 217Sabine Schulz, Sabine Borchard, Tamara Rieder, Carola Eberhagen, Bastian Popper, Josef Lichtmannegger, Sabine Schmitt, and Hans Zischka14 In Vitro Methodologies to Investigate Drug]Induced Toxicities 229Rui F. Simões, Teresa Cunha]Oliveira, Cláudio F. Costa, Vilma A. Sardão, and Paulo J. Oliveira15 Combined Automated Measurement of Respiratory Chain Complexes and Oxidative Stress: A First Step to an Integrated View of Cell Bioenergetics 249Marc Conti, Thierry Delvienne, and Sylvain Loric16 Measurement of Mitochondrial Toxicity by Flow Cytometry 265Padma Kumar Narayanan and Nianyu Li17 MitoChip: A Transcriptomics Tool for Elucidation of Mechanisms of Mitochondrial Toxicity 275Varsha G. Desai, and G. Ronald Jenkins18 Using 3D Microtissues for Identifying Mitochondrial Liabilities 295Simon Messner, Olivier Frey, Katrin Rössger, Andy Neilson, and Jens M. Kelm19 Toward Mitochondrial Medicine: Challenges in Rodent Modeling of Human Mitochondrial Dysfunction 305David A. Dunn, Michael H. Irwin, Walter H. Moos, Kosta Steliou, and Carl A. Pinkert20 Measurement of Oxygen Metabolism In Vivo 315M. P. J. van Diemen, R. Ubbink, F. M. Münker, E. G. Mik, and G. J. Groeneveld21 Detection of Mitochondrial Toxicity Using Zebrafish 323Sherine S. L. Chan and Tucker Williamson22 MiRNA as Biomarkers of Mitochondrial Toxicity 347Terry R. Van Vleet and Prathap Kumar Mahalingaiah23 Biomarkers of Mitochondrial Injury After Acetaminophen Overdose: Glutamate Dehydrogenase and Beyond 373Benjamin L. Woolbright and Hartmut Jaeschke24 Acylcarnitines as Translational Biomarkers of Mitochondrial Dysfunction 383Richard D. Beger, Sudeepa Bhattacharyya, Pritmohinder S. Gill, and Laura P. James25 Mitochondrial DNA as a Potential Translational Biomarker of Mitochondrial Dysfunction in Drug]Induced Toxicity Studies 395Afshan N. Malik26 Predicting Off]Target Effects of Therapeutic Antiviral Ribonucleosides: Inhibition of Mitochondrial RNA Transcription 407Jamie J. Arnold and Craig E. Cameron27 Imaging of Mitochondrial Toxicity in the Kidney 419Andrew M. Hall, Joana R. Martins, and Claus D. Schuh28 Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability 429Anna]Liisa Nieminen, Venkat K. Ramshesh, and John J. Lemasters29 Quantifying Skeletal Muscle Mitochondrial Function In Vivo by 31P Magnetic Resonance Spectroscopy 443Graham J. Kemp  Volume 2List of Contributors xiiiForeword xxvPart 4 Reports from the Clinic 45730 Statin and Fibrate]Induced Dichotomy of Mitochondrial Function 459Viruna Neergheen, Alex Dyson, Luke Wainwright, and Iain P. Hargreaves31 Friend or Foe: Can Mitochondrial Toxins Lead to Similar Benefits as Exercise? 475Sofia Annis, Adeel Safdar, Eduardo Biala, Ayesha Saleem, Housaiyin Li, Priya Gandhi, Zoe Fleischmann, Carmen Castaneda]Sceppa, Jonathan L. Tilly, Dori C. Woods, and Konstantin Khrapko32 Involvement of Mitochondrial Dysfunction on the Toxic Effects Caused by Drugs of Abuse and Addiction 487Daniel José Barbosa, João Paulo Capela, Maria de Lourdes Bastos, and Félix Carvalho33 Drug]Induced Mitochondrial Toxicity during Pregnancy 509Diana Luz Juárez-Flores, Ana Sandra Hernández, Laura Garcia, Mariona Guitart]Mampel, Marc Catalan]Garcia, Ingrid Gonzalez]Casacuberta, Jose César Milisenda, Josep Maria Grau, Francesc Cardellach, Constanza Morén, and Glòria Garrabou34 Mitochondrial Toxicity in Children and Adolescents Exposed to Antiretroviral Therapy 521Antoni Noguera]Julian, Eneritz Velasco]Arnaiz, and Clàudia Fortuny35 Drug]Induced Mitochondrial Cardiomyopathy and Cardiovascular Risks in Children 529Neha Bansal, Mariana Gerschenson, Tracie L. Miller, Stephen E. Sallan, Jason Czachor, Hiedy Razoky, Ashley Hill, Miriam Mestre, and Steven E. Lipshultz36 Role of Mitochondrial Dysfunction in Linezolid]Induced Lactic Acidosis 547Alessandro Santini, Dario Ronchi, Daniela Piga, and Alessandro Protti37 Metformin and Lactic Acidosis 559Jean]Daniel Lalau38 Lessons Learned from a Phase I Clinical Trial of Mitochondrial Complex I Inhibition 563Cecilia C. Low Wang, Jeffrey L. Galinkin, and William R. Hiatt39 Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies 569Whitney S. Gibbs, Natalie E. Scholpa, Craig C. Beeson, and Rick G. Schnellmann40 Mitochondrial Toxicity Induced by Chemotherapeutic Drugs 593Luciana L. Ferreira, Ana Raquel Coelho, Paulo J. Oliveira, and Teresa Cunha]OliveiraPart 5 Environmental Toxicants and Mitochondria 61341 The Mitochondrial Exposome 615Douglas I. Walker, Kurt D. Pennell, and Dean P. Jones42 Central Mitochondrial Signaling Mechanisms in Response to Environmental Agents: Integrated Omics for Visualization 639Young]Mi Go, Karan Uppal, and Dean P. Jones43 Detection of Mitochondrial Toxicity of Environmental Pollutants Using Caenorhabditis elegans 655Laura L. Maurer, Anthony L. Luz, and Joel N. Meyer44 Persistent Organic Pollutants, Mitochondrial Dysfunction, and Metabolic Syndrome 691Hong Kyu Lee and Youngmi Kim Pak45 Cigarette Smoke and Mitochondrial Damage 709Jalal Pourahmad, Marjan Aghvami, Mohammad Hadi Zarei, and Parvaneh NaserzadehIndex 727

Yvonne Will, PhD, is a Senior Director and the Head of Science and Technology Strategy, Drug Safety Research and Development at Pfizer, Connecticut, USA. In addition to the prior edition of this book, she co-edited Drug Discovery Toxicology: From Target Assessment to Translational Biomarkers(Wiley, 2016).James A. Dykens, PhD, oversees EyeCyte Therapeutics, a start-up developing treatments for progressive blinding diseases via targeting mitochondrial dysfunction. He co-edited the first edition of this book.

• Volume 1List of Contributors xviiForeword xxixPart 1 Basic Concepts 11 Contributions of Plasma Protein Binding and Membrane Transporters to Drug]Induced Mitochondrial Toxicity 3Gavin P. McStay2 The Role of Transporters in Drug Accumulation and Mitochondrial Toxicity 15Kathleen M. Giacomini and Huan]Chieh Chien3 Structure–Activity Modeling of Mitochondrial Dysfunction 25Steve Enoch, Claire Mellor, and Mark Nelms4 Mitochondria]Targeted Cytochromes P450 Modulate Adverse Drug Metabolism and Xenobiotic Induced Toxicity 35Haider Raza, F. Peter Guengerich, and Narayan G. AvadhaniPart 2 Organ Drug Toxicity: Mitochondrial Etiology 475 Mitochondrial Dysfunction in Drug]Induced Liver Injury 49Annie Borgne]Sanchez and Bernard Fromenty6 Evaluating Mitotoxicity as Either a Single or Multi]Mechanistic Insult in the Context of Hepatotoxicity 73Amy L. Ball, Laleh Kamalian, Carol E. Jolly, and Amy E. Chadwick7 Cardiotoxicity of Drugs: Role of Mitochondria 93Zoltan V. Varga and Pal Pacher8 Skeletal Muscle Mitochondrial Toxicity 111Eric K. Herbert, Saul R. Herbert, and Karl E. Herbert9 Manifestations of Drug Toxicity on Mitochondria in the Nervous System 133Jochen H. M. Prehn and Irene Llorente]Folch10 Nephrotoxicity: Increasing Evidence for a Key Role of Mitochondrial Injury and Dysfunction and Therapeutic Implications 169Ana Belén Sanz, Maria Dolores Sanchez]Niño, Adrian M. Ramos, and Alberto Ortiz11 Mammalian Sperm Mitochondrial Function as Affected by Environmental Toxicants, Substances of Abuse, and Other Chemical Compounds 185Sandra Amaral, Renata S. Tavares, Sara Escada]Rebelo, Andreia F. Silva, and João Ramalho]SantosPart 3 Methods to Detect Mitochondrial Toxicity: In Vitro, Ex Vivo, In Vivo, Using Cells, Animal Tissues, and Alternative Models 20512 Biological and Computational Techniques to Identify Mitochondrial Toxicants 207Robert B. Cameron, Craig C. Beeson, and Rick G. Schnellmann13 The Parallel Testing of Isolated Rat Liver and Kidney Mitochondria Reveals a Calcium]Dependent Sensitivity to Diclofenac and Ibuprofen 217Sabine Schulz, Sabine Borchard, Tamara Rieder, Carola Eberhagen, Bastian Popper, Josef Lichtmannegger, Sabine Schmitt, and Hans Zischka14 In Vitro Methodologies to Investigate Drug]Induced Toxicities 229Rui F. Simões, Teresa Cunha]Oliveira, Cláudio F. Costa, Vilma A. Sardão, and Paulo J. Oliveira15 Combined Automated Measurement of Respiratory Chain Complexes and Oxidative Stress: A First Step to an Integrated View of Cell Bioenergetics 249Marc Conti, Thierry Delvienne, and Sylvain Loric16 Measurement of Mitochondrial Toxicity by Flow Cytometry 265Padma Kumar Narayanan and Nianyu Li17 MitoChip: A Transcriptomics Tool for Elucidation of Mechanisms of Mitochondrial Toxicity 275Varsha G. Desai, and G. Ronald Jenkins18 Using 3D Microtissues for Identifying Mitochondrial Liabilities 295Simon Messner, Olivier Frey, Katrin Rössger, Andy Neilson, and Jens M. Kelm19 Toward Mitochondrial Medicine: Challenges in Rodent Modeling of Human Mitochondrial Dysfunction 305David A. Dunn, Michael H. Irwin, Walter H. Moos, Kosta Steliou, and Carl A. Pinkert20 Measurement of Oxygen Metabolism In Vivo 315M. P. J. van Diemen, R. Ubbink, F. M. Münker, E. G. Mik, and G. J. Groeneveld21 Detection of Mitochondrial Toxicity Using Zebrafish 323Sherine S. L. Chan and Tucker Williamson22 MiRNA as Biomarkers of Mitochondrial Toxicity 347Terry R. Van Vleet and Prathap Kumar Mahalingaiah23 Biomarkers of Mitochondrial Injury After Acetaminophen Overdose: Glutamate Dehydrogenase and Beyond 373Benjamin L. Woolbright and Hartmut Jaeschke24 Acylcarnitines as Translational Biomarkers of Mitochondrial Dysfunction 383Richard D. Beger, Sudeepa Bhattacharyya, Pritmohinder S. Gill, and Laura P. James25 Mitochondrial DNA as a Potential Translational Biomarker of Mitochondrial Dysfunction in Drug]Induced Toxicity Studies 395Afshan N. Malik26 Predicting Off]Target Effects of Therapeutic Antiviral Ribonucleosides: Inhibition of Mitochondrial RNA Transcription 407Jamie J. Arnold and Craig E. Cameron27 Imaging of Mitochondrial Toxicity in the Kidney 419Andrew M. Hall, Joana R. Martins, and Claus D. Schuh28 Imaging Mitochondrial Membrane Potential and Inner Membrane Permeability 429Anna]Liisa Nieminen, Venkat K. Ramshesh, and John J. Lemasters29 Quantifying Skeletal Muscle Mitochondrial Function In Vivo by 31P Magnetic Resonance Spectroscopy 443Graham J. Kemp  Volume 2List of Contributors xiiiForeword xxvPart 4 Reports from the Clinic 45730 Statin and Fibrate]Induced Dichotomy of Mitochondrial Function 459Viruna Neergheen, Alex Dyson, Luke Wainwright, and Iain P. Hargreaves31 Friend or Foe: Can Mitochondrial Toxins Lead to Similar Benefits as Exercise? 475Sofia Annis, Adeel Safdar, Eduardo Biala, Ayesha Saleem, Housaiyin Li, Priya Gandhi, Zoe Fleischmann, Carmen Castaneda]Sceppa, Jonathan L. Tilly, Dori C. Woods, and Konstantin Khrapko32 Involvement of Mitochondrial Dysfunction on the Toxic Effects Caused by Drugs of Abuse and Addiction 487Daniel José Barbosa, João Paulo Capela, Maria de Lourdes Bastos, and Félix Carvalho33 Drug]Induced Mitochondrial Toxicity during Pregnancy 509Diana Luz Juárez-Flores, Ana Sandra Hernández, Laura Garcia, Mariona Guitart]Mampel, Marc Catalan]Garcia, Ingrid Gonzalez]Casacuberta, Jose César Milisenda, Josep Maria Grau, Francesc Cardellach, Constanza Morén, and Glòria Garrabou34 Mitochondrial Toxicity in Children and Adolescents Exposed to Antiretroviral Therapy 521Antoni Noguera]Julian, Eneritz Velasco]Arnaiz, and Clàudia Fortuny35 Drug]Induced Mitochondrial Cardiomyopathy and Cardiovascular Risks in Children 529Neha Bansal, Mariana Gerschenson, Tracie L. Miller, Stephen E. Sallan, Jason Czachor, Hiedy Razoky, Ashley Hill, Miriam Mestre, and Steven E. Lipshultz36 Role of Mitochondrial Dysfunction in Linezolid]Induced Lactic Acidosis 547Alessandro Santini, Dario Ronchi, Daniela Piga, and Alessandro Protti37 Metformin and Lactic Acidosis 559Jean]Daniel Lalau38 Lessons Learned from a Phase I Clinical Trial of Mitochondrial Complex I Inhibition 563Cecilia C. Low Wang, Jeffrey L. Galinkin, and William R. Hiatt39 Pharmacological Activation of Mitochondrial Biogenesis for the Treatment of Various Pathologies 569Whitney S. Gibbs, Natalie E. Scholpa, Craig C. Beeson, and Rick G. Schnellmann40 Mitochondrial Toxicity Induced by Chemotherapeutic Drugs 593Luciana L. Ferreira, Ana Raquel Coelho, Paulo J. Oliveira, and Teresa Cunha]OliveiraPart 5 Environmental Toxicants and Mitochondria 61341 The Mitochondrial Exposome 615Douglas I. Walker, Kurt D. Pennell, and Dean P. Jones42 Central Mitochondrial Signaling Mechanisms in Response to Environmental Agents: Integrated Omics for Visualization 639Young]Mi Go, Karan Uppal, and Dean P. Jones43 Detection of Mitochondrial Toxicity of Environmental Pollutants Using Caenorhabditis elegans 655Laura L. Maurer, Anthony L. Luz, and Joel N. Meyer44 Persistent Organic Pollutants, Mitochondrial Dysfunction, and Metabolic Syndrome 691Hong Kyu Lee and Youngmi Kim Pak45 Cigarette Smoke and Mitochondrial Damage 709Jalal Pourahmad, Marjan Aghvami, Mohammad Hadi Zarei, and Parvaneh NaserzadehIndex 727