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نویسندگان: Giuseppe Gasparre (editor). Anna Maria Porcelli (editor)
سری:
ISBN (شابک) : 0128196564, 9780128196564
ناشر: Academic Press
سال نشر: 2020
تعداد صفحات: 578
زبان: English
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود)
حجم فایل: 25 مگابایت
در صورت تبدیل فایل کتاب The Human Mitochondrial Genome: From Basic Biology to Disease به فرمت های PDF، EPUB، AZW3، MOBI و یا DJVU می توانید به پشتیبان اطلاع دهید تا فایل مورد نظر را تبدیل نمایند.
توجه داشته باشید کتاب ژنوم میتوکندری انسان: از زیست شناسی پایه تا بیماری نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
ژنوم میتوکندری انسان: از زیستشناسی پایه تا بیماری یک بررسی جامع و بهروز از ژنومیک میتوکندری انسانی ارائه میدهد که تحقیقات پایه را به پزشکی ترجمه در طیفی از انواع بیماریها متصل میکند. در اینجا، کارشناسان بین المللی زیست شناسی ضروری DNA میتوکندری انسان (mtDNA)، از جمله نگهداری، تعمیر، جداسازی و وراثت آن را مورد بحث قرار می دهند. علاوه بر این، تکامل و بهرهبرداری mtDNA، جهشها، روشها و مدلهایی برای مطالعات عملکردی mtDNA مورد بررسی قرار میگیرد. بحث بیماری با رویکردهایی برای استراتژیهای درمانی همراه است، با حوزههای بیماری از جمله سرطان، نورودژنراتیو، مرتبط با سن، کاهش mtDNA، حذف، و بیماریهای جهش نقطهای مورد بحث قرار میگیرد. مکمل نوکلئوزیدها، mitoTALEN ها و نوکلئازهای mitoZNF از جمله رویکردهای درمانی هستند که به طور عمیق مورد بررسی قرار گرفته اند.
با افزایش بودجه برای مطالعات mtDNA، بسیاری از پزشکان و دانشمندان بالینی توجه خود را به ارتباط بیماری mtDNA معطوف کرده اند. این کتاب ابزارها و دانش پیش زمینه مورد نیاز برای انجام تحقیقات جدید و تاثیرگذار در این فضای هیجان انگیز را فراهم می کند، از تمایز یک نوع تعریف کننده هاپلوگروپ یا جهش مرتبط با بیماری تا کاوش مسیرهای درمانی در حال ظهور.
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.
Cover The Human Mitochondrial Genome: From Basic Biology to Disease Copyright Dedication Contents Part 1 Biology of human mtDNA1 Part 2 mtDNA evolution and exploitation109 Part 3 mtDNA mutations171 Part 4 mtDNA-determined diseases and therapies351 List of Contributors Editor’s biographies Preface References Acknowledgments Part 1: Biology of human mtDNA 1 mtDNA replication, maintenance, and nucleoid organization 1.1 Human mitochondrial DNA 1.1.1 Characteristics of mitochondrial DNA 1.1.2 Organization of the human mitochondrial genome 1.2 The process of mtDNA replication 1.2.1 Replication mechanisms 1.2.2 Priming 1.2.3 Elongation of mtDNA replication 1.2.3.1 The mitochondrial DNA polymerase POL γ 1.2.3.2 The mitochondrial DNA helicase Twinkle 1.2.3.3 The mitochondrial single-stranded DNA-binding protein 1.2.3.4 The mitochondrial DNA replisome 1.2.4 Termination of mtDNA replication 1.2.4.1 Primer removal 1.2.4.2 Ligation 1.2.4.3 Separation 1.2.5 Other proteins involved in mtDNA replication 1.3 The mitochondrial dNTP supply 1.4 Mitochondrial nucleoids 1.4.1 Nucleoid composition 1.4.1.1 mtDNA 1.4.1.2 Nucleoid-associated proteins 1.4.2 Nucleoid topology 1.4.3 Nucleoid localization 1.4.4 Nucleoid segregation Acknowledgments References 2 Human mitochondrial transcription and translation 2.1 Introduction 2.2 Coordination of mitochondrial DNA replication and transcription 2.2.1 Overview of mitochondrial DNA replication 2.2.2 The mitochondrial DNA control region 2.2.2.1 The mitochondrial displacement loop 2.2.2.2 The switch between replication and transcription 2.3 Mitochondrial transcription and mitochondrial RNA transactions 2.3.1 Mitochondrial DNA transcription 2.3.1.1 Transcription initiation 2.3.1.2 Transcription elongation 2.3.1.3 Transcription termination 2.3.2 The mitochondrial transcriptome 2.3.3 Mitochondrial RNA-binding proteins and RNA biology 2.3.3.1 Mitochondrial RNA processing 2.3.3.2 Mitochondrial RNA maturation 2.3.3.3 Mitochondrial RNA chaperones and mRNA stability 2.3.3.4 Mitochondrial RNA translation activators 2.4 Mitochondrial translation 2.4.1 The mitochondrial translation machinery 2.4.1.1 Mitoribosome structure 2.4.1.2 Mitoribosome biogenesis 2.4.2 Mitochondrial protein synthesis 2.4.2.1 Mitochondrial translation initiation 2.4.2.2 Mitochondrial translation elongation 2.4.2.3 Mitochondrial translation termination and mitoribosome recycling 2.4.2.4 Cotranslational membrane insertion of newly synthesized polypeptides 2.5 Compartmentalization of gene expression 2.5.1 Mitochondrial DNA nucleoids 2.5.2 Mitochondrial RNA granules 2.5.3 Mitochondrial RNA degradosome References 3 Epigenetic features of mitochondrial DNA 3.1 A brief overview of mitochondrial DNA 3.2 Does cytosine methylation occur in mtDNA? 3.3 Bisulfite sequencing analysis of mtDNA 3.4 Estimation of mtDNA methylation with McrBC endonuclease 3.5 Investigation of 5mC in mtDNA by nucleoside liquid chromatography/mass spectrometry 3.6 Epigenetic features of mammalian mtDNA Acknowledgments References 4 Heredity and segregation of mtDNA 4.1 Introduction 4.2 General principles of mtDNA segregation 4.3 Uniparental maternal inheritance of mitochondrial DNA 4.4 Paternal leakage during mtDNA inheritance 4.5 mtDNA mutations—homoplasmy versus heteroplasmy 4.6 Germline segregation of mtDNA mutations and the genetic bottleneck 4.7 Purifying selection against mtDNA mutations in the germline 4.8 Somatic mtDNA mutations and clonal expansion 4.9 Conclusions References Part 2: mtDNA evolution and exploitation 5 Haplogroups and the history of human evolution through mtDNA 5.1 Early restriction fragment length polymorphism studies 5.2 The advent of polymerase chain reaction in the mtDNA world 5.3 Haplogroup nomenclature of human mtDNA 5.4 The survey of entire mitogenomes 5.5 The “Out of Africa Exit” 5.6 The first peopling of the Americas 5.7 The peopling of an island in the Mediterranean Sea References 6 Human nuclear mitochondrial sequences (NumtS) 6.1 NumtS definition and introduction 6.2 NumtS discovery 6.3 NumtS detection 6.3.1 In silico human NumtS detection based on reference genomes 6.3.2 Detection of sample-specific NumtS 6.3.3 In vitro NumtS identification 6.4 Numtogenesis: Mechanisms of NumtS insertion 6.5 NumtS variability and polymorphisms 6.6 The role of NumtS in mtDNA sequencing and disease 6.7 NumtS annotation: Current and future roles of NumtS References 7 mtDNA exploitation in forensics 7.1 Introduction 7.2 mtDNA typing in historical forensic identification 7.3 mtDNA sequencing in forensic practice 7.3.1 Extraction 7.3.2 mtDNA quantification by real-time PCR 7.3.3 Targeted region and PCR amplification 7.3.4 mtDNA sequencing 7.3.5 Rapid screening assay for mtDNA type 7.3.6 Massive parallel sequencing of full mitochondrial genome 7.4 Data analysis, alignment, and haplotype notation 7.4.1 Alignment 7.4.2 Notation for forensics purposes 7.4.3 Heteroplasmy 7.5 Interpretation of mtDNA results 7.5.1 Sequence comparison 7.5.2 Statistical evaluation: weight of evidence 7.6 Mitochondrial DNA population databases used in forensics 7.7 Guidelines and recommendations References Part 3: mtDNA mutations 8 Human mitochondrial DNA repair 8.1 Base excision repair 8.2 Repair of bulky lesions 8.3 Double-strand break repair 8.4 Mismatch repair 8.5 Translesion synthesis 8.6 Concluding remarks References 9 Mechanisms of onset and accumulation of mtDNA mutations 9.1 Mitochondrial DNA abnormalities 9.1.1 Primary mitochondrial DNA mutants 9.1.1.1 Rearrangements: deletions and duplications 9.1.1.2 Mitochondrial DNA point mutants 9.2 Criteria to designate a primary mtDNA mutation as pathological 9.3 Clinical and biochemical correlates 9.4 Mitochondrial genetic rules 9.5 Selection and counterselection of deleterious mtDNA variants 9.5.1 Phenotypic selection of fully functional mtDNAs 9.5.2 Propagation of dysfunctional mitochondria—misuse of the natural process of coupling mitochondrial mass to energy demand 9.5.3 Selfish mechanisms 9.5.4 Metabolic configuration and nutrient availability 9.6 Genetic drift 9.7 Mitochondrial DNA selection—more or less? 9.8 Stable heteroplasmy—the persistence of a fixed proportion of mutant and wild-type mtDNA 9.9 Mitochondrial DNA maintenance disorders 9.10 Ribonucleotide incorporation—a new mtDNA abnormality and a potential precursor or mitigator of mtDNA deletions and dep... 9.11 Overlaps between nuclear defects in the mtDNA maintenance system and primary mtDNA mutants 9.12 A mitochondrial DNA network and its implications for heteroplasmy Acknowledgments References 10 Mitochondrial DNA mutations and aging 10.1 Introduction 10.2 Old and new mitochondrial theories of aging—how changes in mtDNA contribute to aging? 10.3 Mitochondrial genetics from the perspective of aging 10.4 mtDNA deletions and aging 10.4.1 The origin of mtDNA deletions 10.4.2 How do mtDNA deletions expand during aging? 10.4.3 Do mtDNA deletions play a role in aging? 10.5 mtDNA point mutations 10.5.1 MtDNA point mutations occur during aging 10.5.2 The origin of somatic mtDNA point mutations during aging: oxidative stress versus replication errors? 10.5.3 Oxidative damage 10.5.4 DNA polymerases 10.5.5 Is mtDNA susceptible to oxidative damage? 10.5.6 Origin of mtDNA mutations—evidence from animal models 10.5.7 When are point mutations generated, and how do they expand? 10.6 How do somatic mtDNA mutations lead to aging? 10.6.1 Tissue-specific consequences of mtDNA mutations during aging 10.7 mtDNA mutations and aging of stem cells 10.8 Conclusions Acknowledgments References 11 Methods for the identification of mitochondrial DNA variants 11.1 Introduction to human mtDNA variants detection 11.2 Techniques for detecting mitochondrial variants 11.2.1 Polymerase chain reaction–based methods and mtDNA rearrangements detection 11.2.1.1 Polymerase chain reaction restriction fragment length polymorphism 11.2.1.2 Southern blotting and long-range polymerase chain reaction 11.2.1.3 Pyrosequencing 11.2.1.4 Quantitative polymerase chain reaction 11.2.1.5 Single molecule–based detection techniques 11.2.2 Broad-spectrum techniques for detection of variants in whole mtDNA genomes 11.2.2.1 Single-strand conformation polymorphism 11.2.2.2 Denaturing high-performance liquid chromatography 11.2.2.3 Sanger sequencing 11.2.2.4 Microarrays 11.2.2.5 Second-generation sequencing 11.2.2.6 Third-generation sequencing 11.3 Challenges in mitochondrial variant studies 11.3.1 Mitochondrial DNA isolation 11.3.2 NumtS contamination 11.4 Bioinformatics strategies to detect mitochondrial variants and heteroplasmy 11.4.1 Reads mapping and genome assembly 11.4.2 Mitochondrial variant calling 11.4.3 Mitochondrial phylogenetic analysis References 12 Bioinformatics resources, databases, and tools for human mtDNA 12.1 Introduction to human mtDNA variability (Wallace DC and Attimonelli M) 12.2 Human mtDNA genomes and variants 12.2.1 Primary databases: GenBank/ENA/DDBJ (Attimonelli M) 12.2.2 MITOMAP (Lott MT, Procaccio V, and Zhang S) 12.2.2.1 Variant status in MITOMAP 12.2.2.2 Haplogroup assignment in MITOMAP 12.2.2.3 Allele search function in MITOMAP 12.2.2.4 Analyzing mtDNA variability using MITOMASTER 12.2.2.5 MitoTIP 12.3 The Human MitoCompendium: HmtDB, HmtVar, and HmtPhenome (Attimonelli M, Preste R, and Vitale O) 12.3.1 HmtDB 12.3.1.1 HmtDB API 12.3.2 HmtVar (Preste R, Vitale O, and Attimonelli M) 12.3.2.1 HmtVar variants pathogenicity assessment (Attimonelli M and Vitale O) 12.3.3 HmtPhenome (Preste R and Attimonelli M) 12.4 MSeqDR—Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium (Lott M) 12.4.1 MvTool 12.5 Other specialized human mitochondrial databases (Attimonelli M and Preste R) 12.6 Tools for variant annotations (Attimonelli M and Preste R) 12.6.1 HmtNote 12.6.2 HaploGrep 12.6.3 MitImpact3D 12.6.4 PON-mt-tRNA [87] 12.7 Nuclear encoded mitochondrial genes databases (Vitale O and Attimonelli M) References Further reading 13 Methods and models for functional studies on mtDNA mutations 13.1 Introduction 13.2 Models for the study of mtDNA mutations: in vitro models 13.2.1 Human primary cell lines 13.2.2 Cybrids 13.2.3 Patient-specific induced pluripotent stem cells 13.2.4 Yeast 13.3 Animal models 13.3.1 Caenorhabditis elegans 13.3.2 Drosophila melanogaster 13.3.2.1 ATP6 mutant 13.3.2.2 CoI mutants 13.3.2.3 ND2 mutants 13.3.2.4 CoII mutant 13.3.3 Mice 13.3.3.1 mtDNA deletions 13.3.3.2 mt-Co1 13.3.3.3 mt-Nd6 13.3.3.4 mt-tK (tRNALys) 13.3.3.5 mt-tA (tRNAAla) 13.3.3.6 PolgA 13.3.3.7 Twnk 13.3.3.8 Mgme1 13.4 Methods for assessment of functional defects induced by mtDNA alterations 13.4.1 OXPHOS complexes activity 13.4.1.1 Spectrophotometric methods 13.4.1.1.1 Sample preparation 13.4.1.1.2 NADH:ubiquinone oxidoreductase activity (CI activity) 13.4.1.1.3 Succinate:ubiquinone oxidoreductase activity (CII activity) 13.4.1.1.4 Ubiquinol:cytochrome c oxidoreductase activity (CIII activity) 13.4.1.1.5 Cytochrome c oxidoreductase activity (CIV activity) 13.4.1.1.6 NADH:cytochrome c oxidoreductase (CI+III activity) 13.4.1.1.7 Succinate:cytochrome c oxidoreductase (CII+III activity) 13.4.1.1.8 Hydrolytic activity of ATP synthase (CV activity) 13.4.1.1.9 Citrate synthase activity 13.4.1.2 Immunocapture-based assays 13.4.2 Oxygen consumption 13.4.2.1 Classic Clark-type electrode methods 13.4.2.2 High-resolution respirometry 13.4.2.3 Microrespirometry on multiwell plate 13.4.3 Determination of mitochondrial membrane potential 13.4.4 ATP production 13.4.5 Reactive oxygen species measurement 13.4.6 Blue Native Polyacrylamide Gel Electrophoresis References Part 4: mtDNA-determined diseases and therapies 14 Mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations 14.1 Clinical syndromes of mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations 14.1.1 Exercise intolerance 14.1.2 Kearns-Sayre syndrome 14.1.3 Leber-dystonia 14.1.4 Leber hereditary optic neuropathy 14.1.5 Maternally inherited diabetes and deafness 14.1.6 Maternally inherited Leigh syndrome 14.1.7 Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes 14.1.8 Mitochondrial myopathy and cardiomyopathy 14.1.9 Myoclonic epilepsy with ragged red fibers 14.1.10 Neurogenic muscle weakness, ataxia, retinitis pigmentosa 14.1.11 Nonsyndromic sensorineural hearing loss 14.1.12 Pearson marrow pancreas syndrome 14.1.13 Progressive external ophthalmoplegia/progressive external ophthalmoplegia plus 14.1.14 Reversible infantile mitochondrial myopathy 14.2 Molecular genetics of mitochondrial DNA single large-scale deletions and point mutations 14.3 Diagnostic approach to mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations 14.3.1 Laboratory tests 14.3.2 Neuroimaging 14.3.3 Skeletal muscle histochemistry, electron microscopy, and respiratory chain biochemistry 14.3.4 Genetic testing 14.4 Management of mitochondrial DNA-related diseases associated with single large-scale deletions and point mutations 14.4.1 Supportive therapies 14.4.2 Vitamins and cofactors 14.4.3 Emerging therapies 14.4.4 Reproductive options Acknowledgments References 15 Nuclear genetic disorders of mitochondrial DNA gene expression 15.1 Introduction 15.2 Mechanisms of mtDNA replication 15.3 Defects of mtDNA replication 15.3.1 Mutations in POLG 15.3.2 Mutations in TWNK 15.3.3 Mutations in DNA2 15.3.4 Mutations in MGME1 15.4 Maintenance of dNTP pool 15.5 Defects of the dNTP salvage pathway and nucleotide metabolism 15.5.1 Mutations in TK2 15.5.2 Mutations in RRM2B 15.5.3 Mutations in MPV17 15.6 Mechanism of mitochondrial transcription 15.7 Defects of mitochondrial transcription 15.7.1 Mutations in TFAM 15.7.2 Mutations in TFB2M 15.8 Transcript processing 15.9 Defects of maturation of pre mt-RNA 15.9.1 Mutations in RNase P complex (MRPP1, 2, 3) 15.9.2 Mutations in RNase Z (ELAC2) 15.10 mt-mRNA maturation and turnover 15.11 Defects of mt-mRNA maturation and turnover 15.11.1 Mutations in MTPAP 15.11.2 Mutations in LRPPRC 15.12 mt-tRNA maturation 15.13 Defects of mt-tRNA maturation and modification 15.13.1 Mutations in TRNT1 15.13.2 Mutations in PUS1 15.13.3 Mutations in MTO1 and GTPBP3 15.13.4 Mutations in TRMU 15.13.5 Mutations in TRIT1 15.13.6 Mutations in mitochondrial aminoacyl-tRNA synthetases 15.14 mt-rRNA maturation 15.15 Defects of mt-rRNA maturation, modification, and stability 15.15.1 Mutations in MRM2 15.15.2 Mutations in FASTKD2 15.16 Mechanism of mitochondrial translation 15.17 Mutations in mitoribosomal proteins 15.18 Defects of translation initiation 15.18.1 Mutations in MTFMT 15.18.2 Mutations in RMND1 15.19 Defects of translation elongation 15.19.1 Mutations in GFM1 15.19.2 Mutations in TSFM 15.20 Defects of translation termination and mitoribosome recycling 15.20.1 Mutations in C12orf65 15.20.2 Mutations in GFM2 15.21 Defects of translational activation and coupling 15.21.1 Mutations in TACO1 15.21.2 Mutations in COA3 and C12orf62 15.22 IMM insertion of mtDNA-encoded OXPHOS proteins 15.22.1 Mutations in OXA1L Acknowledgments References 16 mtDNA maintenance: disease and therapy 16.1 Introduction 16.2 Defects in mtDNA replisome 16.3 Defects in mitochondrial nucleotides pool balance 16.4 Defects in mitochondrial dynamics 16.5 Defect in nucleoid proteins 16.6 Experimental therapies 16.7 General pharmacological approaches 16.7.1 Targeting mitochondrial biogenesis 16.7.2 Targeting mTOR pathway 16.8 Disease-tailored therapies 16.8.1 Nucleos(t)ide supplementation therapies 16.8.2 Clearance of toxic metabolites 16.8.3 Enzyme replacement 16.8.4 Platelet infusion 16.8.5 Hematopoietic stem cell transplantation 16.8.6 Erythrocytes encapsulated thymidine phosphorylase 16.8.7 Liver transplant: tissue-specific disorder and source of enzyme replacement 16.8.8 Gene therapy Acknowledgments References 17 mtDNA mutations in cancer 17.1 The landscape of mtDNA mutations in cancer 17.2 Functional effects of mtDNA mutations in solid cancers 17.2.1 mtDNA mutations and metabolic adaptation 17.2.2 MtDNA mutations and hypoxic stress 17.2.3 mtDNA mutations and metastatic progression 17.3 The fate of severely pathogenic mtDNA mutations in progressing solid tumors 17.3.1 Molecular mechanisms behind selection and purification of mtDNA mutations in cancer 17.3.2 Compensatory mechanisms to overcome mitochondrial dysfunction 17.3.3 MtDNA mutations in oncocytomas: an exception from the rule 17.4 Clinical potential of cancer-associated mtDNA mutations 17.4.1 MtDNA mutations and cancer treatment 17.4.1.1 Chemotherapy 17.4.1.2 Radiotherapy 17.4.1.3 Interventions in cancer therapy based on mitochondrial functional status 17.4.2 Cancer-specific mtDNA mutations as markers of tumor progression 17.5 Insights from next generation sequencing and bioinformatics approaches 17.5.1 Technical pitfalls and false discoveries of the past 17.5.2 Methodological recommendations for mtDNA mutation analysis in the advent of next generation sequencing in oncology 17.5.3 The influence of big data on what we know on mtDNA mutations in cancer References 18 MitoTALENs for mtDNA editing 18.1 Introduction 18.2 The use of specific endonucleases to target mtDNA 18.3 The use of mitoTALENs to target mtDNA 18.4 Structure of mitoTALENs 18.5 MitoTALENs targeting mutations in cybrids 18.6 MitoTALENs in a heteroplasmic mouse model carrying a tRNAAla mutation 18.7 MitoTALENs and induced pluripotent stem cells 18.8 Other uses of mitoTALENs 18.8.1 MitoTALENs in germline transmission 18.8.1.1 MitoTALENs to study mtDNA replication 18.8.2 MitoTevTAL nuclease 18.9 Pros and cons of using mitoTALENs for gene therapy 18.9.1 Specificity and mtDNA depletion 18.9.2 Off-target sequences in the nucleus 18.9.3 Easy design of new recognition sites 18.9.4 MitoTALEN gene size 18.9.5 The future of mitoTALENs as therapy References 19 Mitochondrially targeted zinc finger nucleases 19.1 Introduction 19.2 Zinc finger domain—structure and interaction with DNA 19.3 Designer zinc fingers 19.4 Chimeric zinc finger proteins—birth of zinc finger nuclease 19.5 Manipulation of the mammalian mitochondrial genome with mtZFNs 19.5.1 The first step 19.5.2 In vivo use of mtZFNs 19.6 Concluding remarks Acknowledgments References 20 Mitochondrial movement between mammalian cells: an emerging physiological phenomenon 20.1 Introduction 20.2 Cell-to-cell transfer of mitochondria with mtDNA: a brief overview 20.3 Translational benefits of mitochondrial transfer 20.3.1 Mitochondrial transfer between cells 20.3.1.1 Mitochondrial transfer into tumor cells 20.3.1.2 Mitochondrial transfer into normal cells 20.3.1.3 Mitochondrial donation therapy to prevent mitochondrial diseases in offspring 20.3.2 Transfer of isolated mitochondria 20.3.2.1 Ischemic heart disease 20.3.2.2 Neurodegenerative disorders and ischemic stroke 20.3.2.3 Behavioral disorders 20.3.2.4 Cancer sensitization to treatment 20.4 Mechanisms of mitochondrial transfer 20.5 Mito-nuclear crosstalk: potential consequences of mitochondrial transfer/transplantation 20.6 Concluding statement Acknowledgments References Index Back Cover