1;Preface;5 2;Contents;8 3;Chapter 1: Basic Mitochondrial Genetics, Bioenergetics, and Biogenesis;16 3.1;Introduction;16 3.2;The Mitochondrion;17 3.3;Contrasting Features of Mitochondrial and Nuclear Genetics;18 3.4;Mitochondrial Genomic Structure and Organization;26 3.5;Mitochondrial Microsatellites and D310;27 3.6;Mitochondrial Pseudogenes;28 3.7;The Respiratory Chain;29 3.7.1;The Electron Transport Chain;29 3.7.2;Coupling of the Proton Gradient with Oxidative Phosphorylation;34 3.7.3;The Respiratory Chain and Reactive Oxygen Species Production;34 3.8;Mitochondrial Biogenesis;35 3.8.1;Mitochondrial Genome Replication;35 3.8.2;Mitochondrial Genome Transcription;37 3.8.2.1;Mitochondrial Transcription Initiation Machinery;37 3.8.2.2;Mitochondrial Transcripts;38 3.8.2.3;Mitochondrial RNA Processing;38 3.8.2.4;Mitochondrial RNA Turnover;39 3.8.2.5;Translation of Mitochondrial Messenger RNAs;40 3.9;Control of Mitochondrial Biogenesis;41 3.9.1;Hormonal Control;41 3.9.2;Nuclear Respiratory Factors;42 3.9.3;Peroxisomal Proliferator Activator Receptor Gamma Co-Activator-1a;43 3.9.4;Regulation of PGC-1;43 3.9.5;PGC-1a-Related Coactivator;45 3.9.6;Myc Oncogene and Mitochondrial Biogenesis;45 3.10;Import of Nuclear-Encoded Proteins into Mitochondria;45 3.11;Mitochondrial Import of Cytosolic Transfer RNA;46 3.12;Conclusion;46 3.13;References;47 4;Chapter 2: The Warburg Phenomenon and Other Metabolic Alterations of Cancer Cells;52 4.1;Introduction;52 4.2;Bioenergetics of Normal Cells;53 4.3;The Crabtree Effect;53 4.4;The Warburg Phenomenon;55 4.5;Molecular Basis of the Warburg Phenomenon;59 4.5.1;HK and Glycolysis;61 4.5.2;The PI3K/AKT Signaling Pathway and Glycolysis;62 4.5.3;The MYC Oncogene and Glycolysis;63 4.5.4;Hypoxia-Inducible Factor Pathway and Glycolysis;64 4.5.4.1;Regulation of Hypoxia-Inducible Factor;64 4.5.4.2;Regulation of Glycolysis and Mitochondrial Functions by Hypoxia-Inducible Factor;66 4.5.5;P53 and Glycolysis;68 4.6;Glutamine Metabolism in Cancer Cells;69 4.7;Lipid Metabolism in Cancer Cells;70 4.8;Citrate Metabolism by Prostate Glandular Epithelial Cells;71 4.9;Clinical Implications of Altered PCa Metabolism;72 4.9.1;Diagnostic Imaging of PCa;73 4.9.2;Screening for PCa Using Biofluids;74 4.9.3;PCa Prevention and Treatment;74 4.10;Conclusion;75 4.11;References;75 5;Chapter 3: Mitochondrial Control of Apoptosis and Cancer;80 5.1;Introduction;80 5.2;Cell Death Processes: The Conundrum of Semantics;81 5.3;Physiologic Importance of Apoptosis;82 5.4;Caspase Cascade;82 5.5;The Intrinsic or Mitochondrial Apoptotic Pathway;83 5.5.1;Mitochondrial Membrane Permeabilization;83 5.5.2;BCL-2 Family Members and Regulation of Mitochondrial Membrane Permeabilization;85 5.5.3;The Execution of Mitochondrial Apoptosis;88 5.5.4;Viral Control of Mitochondrial Apoptosis;89 5.5.5;Regulation of Intrinsic Apoptosis by Signaling Pathways;90 5.5.6;Mitochondrial Fission and Apoptosis;93 5.6;The Extrinsic Apoptotic Pathway;93 5.7;Evasion of Apoptosis by Cancer Cells;94 5.7.1;Cancer as a Defect in Apoptosis;95 5.7.2;Intrinsic Apoptotic Pathway Alterations in Cancer;95 5.7.3;Extrinsic Apoptotic Pathway Alterations in Cancer;97 5.8;Mitochondrial Genetic Defects and Apoptosis;98 5.9;Conclusion;100 5.10;References;100 6;Chapter 4: Mitochondrial-to-Nuclear Communications in Cancer;106 6.1;Introduction;106 6.2;Succinate Dehydrogenase and Fumarate Hydratase Mutations and Cancer;107 6.2.1;SDH Mutations and Cancer;108 6.2.1.1;Paragangliomas;108 6.2.1.2;Genetics and Clinical Features of PGL;109 6.2.1.3;SDH Mutations in Other Cancers;113 6.2.2;Genetics and Clinical Features of Fumarate Hydratase Mutations;113 6.2.2.1;Fumarate Hydratase Mutations in Other Cancers;115 6.2.3;Genetic Testing and Counseling for SDH and FH Mutations;115 6.2.3.1;SDH Mutations;115 6.2.3.2;Fumarate Hydratase Mutations;117 6.2.4;Mechanism of Tumor Induction by SDH and Fumarate Hydratase Mutations;118 6.3;Mitochondria-to-Nuclear Stress Signaling in Cancer;121 6.4;Nuclear Integration of