Mitochondrial Disorders: From Pathophysiology to Acquired Defects

G. SERRATRICE This book is new and original. For some decades mitochondriopathies have been extensively studied: morphology, biochemistry, genetics. However these studies mainly concerned encephalopathies and myopathies related to mito- chondrial disorders. In this book the field of mitochondrial cytopathies is largely extended to "Mitochondrial Medicine". Very new data are gathered. A new step is jumped. Many medical specialities are concerned. Part I is devoted to mitochondrial biology: the mitochondrial machinery, the dysfunction of mitochondrial in elderly: cell decline, deleterious effects of oxidative stress in ageing, especially dysfunction of cardiac mitochondria, as well mitochondrial involvement in neurodegeneration. An attractive chapter concerns the implication of apoptosis, the programmed cell death, linked to cytochrome oxidase defect. Iatrogenic mitochondrial diseases are studied in Part II either due to a sen- sitivity to some drug or especially induced by antiretroviral drugs. Several drugs lead to a mitochondrial toxicity: antiepileptic treatment, anticancer drugs. Mitochondrial damage involving mainly the mitochondrial DNA is frequent in patients treated for several years by antiretroviral drugs, with absolute deple- tion of mitochondrial DNA. Some patients with severe lactic acidosis and mul- tiple organ failures may be improved by carnitine. Special problemes arise in newborn and in perinatal exposure to antiretroviral drugs. In case of treated mother a mitochondrial disease could occur in non infested newborn.

Table of Contents:
Introduction.- I. Mitochondrial Biology: 1. The Mitochondrial Machinery. 2. Mitochondria in Neurodegeneration. 3. Apoptosis and Oxidative Stress in Mitochondrial Disorders. 4. Mitochondria and Ageing. 5. Cardiac Mitochondrial Dysfunction in Ageing and in Ischemia/Reperfusion. Role of Oxygen Free Radicals and Cardiolipin. 6. Deregulation of Mitochondrial Apoptosis in Cancer.- II. Iatrogenic Mitochondrial Diseases: 7. Drug Induced Hepatotoxicity and Mitochondrial Dysfunction. 8. The Carnitine System Involvement in Mitochondrial Pharmacologic Sensitivity. 9. Mitochondrial Toxicity of Antiretroviral Drugs. 10. Mitochondrial Damage in HIV Patients Treated with Highly Active Antiretroviral Therapy. 11. Hyperlactatemia and HIV-infected Patients with Nucleoside Analog Reverse-Transcriptase Inhibitors Treatment: The Clermont HIV Cohort Study. 12. Severe Lactic Acidosis and Multiple Organ Failure in HIV Patients Treated with Nucleoside Analogues Reverse Transcriptase Inhibitors: A Pilot Study of Treatment with L-Carnitine. 13. Mitochondrial Dysfunction in Perinatal Exposure to Antiretroviral Nucleoside Analogues. 14. Mitochondrial Myopathy in Non-infected New-Born from HIV-1 Mothers Treated with Antiretroviral Drugs.- III. Mitochondrial Medicine: 15. Neurological Features of Genetic and Acquired Metabolic Mitochondrial Defects. 16. Clinical Heterogeneity Associated to Dysfunction of Mitochondrial DNA: The example of the 3243 MELAS Mutation. 17. Inborn and Acquired Mitochondrial Leucodystrophy. 18. Mitochondrial Dysfunction, Epilepsy, and Antiepileptic drugs. 19. Friedreich Ataxia as an Example of the Dual Genome Control of Mitochondrial Function. 20. How Wide are Mitochondria Involved in Exercise Intolerance? 21. Mitochondrial Defects in Myositis and Inclusion Body Myopathies. 22. Mitochondrial Dysfunction and the Gastrointestinal System. 23. Mitochondrial Diabetes: Clinical Specificity and Diagnosis. 24. Mitochondrial Featuring in Kidney Disorders and Myelodysplastic Syndromes.- IV. Treatment: 25. Treatment of Mitochondrial Diseases.