Physiology and pathophysiology of mitochondrial DNA

Abstract

Mitochondria are the only organelles in animal cells which possess their own genomes. Mitochondrial DNA (mtDNA) alterations have been associated with various human conditions. Yet, their role in pathogenesis remains largely unclear. This review focuses on several major features of mtDNA: (1) mtDNA haplogroup, (2) mtDNA common deletion, (3) mtDNA mutations in the control region or D-loop, (4) mtDNA copy number alterations, (5) mtDNA mutations in translational machinery, (6) mtDNA mutations in protein coding genes (7) mtDNA heteroplasmy. We will also discuss their implications in various human diseases.

Fig. 2.1

Human mitochondrial genome. It encodes 13 peptides, 22 tRNA and 2 rRNA. The D-loop contains mtDNA replication origin and transcription promoters. The 4,977-bp common deletion is indicated

Fig. 2.2

Classification of mtDNA haplogroups in Wenzhou population. The defining sites utilized in this study are listed in the branches. “d” indicates a deletion; “9bpd” indicates a 9bp deletion in the intergenic mtDNA region between nucleotides 8,195–8,316

Fig. 2.3

mtDNA tRNA/rRNA mutation map. ADPD Alzheimer’s Disease and Parkinsons’s Disease, CIPO Chronic Intestinal Pseudoobstruction with myopathy and Ophthalmoplegia, CPEO Chronic Progressive External Ophthalmoplegia, DEMCHO Dementia and Chorea, DM Diabetes Mellitus, DMDF Diabetes Mellitus & Deafness, EXIT exercise intolerance, FICP Fatal Infantile Cardiomyopathy Plus, a MELAS-associated cardiomyopathy, HCM Hypertrophic Cardio Myopathy, LS Leigh Syndrome, MELAS Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, MERRF Myoclonic Epilepsy and Ragged Red Muscle Fibers, MHCM Maternally Inherited Hypertrophic Cardiomyopathy, MICM Maternally Inherited Cardiomyopathy, MM Mitochondrial Myopathy, SNHL Sensorineural Hearing Loss

Fig. 2.4

mtDNA coding region mutation map. AD Alzheimer’s Disease, ADPD Alzheimer’s Disease and Parkinsons’s Disease, CPEO Chronic Progressive External Ophthalmoplegia, DM Diabetes Mellitus, EXIT exercise intolerance, FBSN Familial Bilateral Striatal Necrosis, HCM Hypertrophic Cardio Myopathy, LHON Leber Hereditary Optic Neuropathy, LS Leigh Syndrome, MELAS Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes, MM Mitochondrial Myopathy, NAION Nonarteritic Anterior Ischemic Optic Neuropathy, NARP Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa, SIDA Sideroblastic Anemia, SNHL Sensorineural Hearing Loss