The Human Mitochondrial Genome

The Human Mitochondrial Genome: From Basic Biology to Disease offers a comprehensive, up-to-date examination of human mitochondrial genomics, connecting basic research to translational medicine across a range of disease types. Here, international experts discuss the essential biology of human mitochondrial DNA (mtDNA), including its maintenance, repair, segregation, and heredity. Furthermore, mtDNA evolution and exploitation, mutations, methods, and models for functional studies of mtDNA are dealt with. Disease discussion is accompanied by approaches for treatment strategies, with disease areas discussed including cancer, neurodegenerative, age-related, mtDNA depletion, deletion, and point mutation diseases. Nucleosides supplementation, mitoTALENs, and mitoZNF nucleases are among the therapeutic approaches examined in-depth.

With increasing funding for mtDNA studies, many clinicians and clinician scientists are turning their attention to mtDNA disease association. This book provides the tools and background knowledge required to perform new, impactful research in this exciting space, from distinguishing a haplogroup-defining variant or disease-related mutation to exploring emerging therapeutic pathways.

• Fully examines recent advances and technological innovations in the field, enabling new mtDNA studies, variant and mutation identification, pathogenic assessment, and therapies
• Disease discussion accompanied by diagnostic and therapeutic strategies currently implemented clinically
• Outlines and discusses essential research protocols and perspectives for young scientists to pick up
• Features an international team of authoritative contributors from basic biologists to clinician-scientists

Active researchers in biochemistry, molecular biology, cell biology, oncology, neurology, neuroscience, and pharmacology; clinician scientists

Part 1 – Biology of human mtDNA
1. MtDNA replication, maintenance and nucleoid organization
Sjoerd Wanrooij
2. Human mitochondrial transcription and translation
Antonio Barrientos
3. Epigenetic features of mitochondrial DNA
Takehiro Yasukawa, Shigeru Matsuda and Dongchon Kang
4. Heredity and Segregation of mtDNA
Patrick F. Chinnery

Part 2 - MtDNA evolution and exploitation
5. Haplogroups and the history of human evolution through mtDNA
Antonio Torroni, Alessandro Achilli, Anna Olivieri and Ornella Semino
6. Human Nuclear mitochondrial Sequences (NumtS)
Marcella Attimonelli and Francesco Maria Calabrese
7. MtDNA exploitation in forensics
Adriano Tagliabracci and Chiara Turchi

Part 3 – MtDNA mutations
8. Human mitochondrial DNA repair
Elaine Ayres Sia and Alexis Stein
9. Mechanisms of onset and accumulation of mtDNA mutations
Antonella Spinazzola and Ian Holt Sr.
10. Mitochondrial DNA mutations and ageing
Aleksandra Trifunovic
11. Methods for the identification of mitochondrial DNA variants
Marcella Attimonelli, Claudia Calabrese, Aurora Gomez Duran and Aurelio Reyes
12. Bioinformatics resources, databases, and tools for human mtDNA
Marcella Attimonelli, Marie Lott, Roberto Preste, Douglas C. Wallace, Vincent Procaccio, Shiping Zhang and Ornella Vitale
13. Methods and models for functional studies on mtDNA mutations
Luisa Iommarini, Anna Maria Ghelli and Francisca Diaz

Part 4 – MtDNA-determined diseases
14. Mitochondrial DNA point mutation diseases
Shamima Rahman and Rob Pitceathly
15. Nuclear genetic disorders of mitochondrial DNA gene expression
Robert W. Taylor
16. mtDNA maintenance: disease and therapy
Caterina Garone
17. MtDNA mutations in cancer
Ivana Kurelac, Giuseppe Gasparre, Giulia Girolimetti, Monica De Luise and Anna Maria Porcelli
18. MitoTALENs for mtDNA editing
Carlos Moraes and Sandra Bacman
19. Mitochondrially-Targeted Zinc Finger Nucleases
Michal Minczuk
20. Mitochondrial movement between mammalian cells: an emerging physiological phenomenon
Michael V. Berridge