chapter  11
20 Pages

Cybrids in the Study of Animal Mitochondrial Genetics and Pathology

Introduction .......................................................................... 540 Historical Overview ............................................................. 541

Early Studies with Plants and Simple Eukaryotes ........................................................ 541

Early Mammalian Cell Cybrids: CAPR and Others................................................................ 542

ρ0 Cells: Freedom from Drug-Selectable Markers .... 542 Cybrid Modeling of Pathogenic mtDNA Mutations

Associated with Human Disease: Successes and Limitations ........................................................... 544

Mouse Cell mtDNA Mutants and Cybrids......................... 546 Xenomitochondrial Cybrids ........................................ 547

Some Burning Questions for Cybrids................................. 549 Complementation of Heteroplasmic

mtDNA Mutants............................................... 549

mtDNA Contributions to Polygenic Disorders and Tissue-Specific Effects .............................. 549

Unknown mtDNA and OXPHOS Functions ............. 550 References............................................................................. 551

INTRODUCTION

Margaret Nass first determined that threads of DNA existed in animal mitochondria (1,2) and, around the same time, Gibor demonstrated DNA in chloroplasts (3,4); these events began the resolution of mysteries surrounding ideas of “cytoplasmic inheritance” arising from careful observations made with plants 50 years earlier. Ten years following the discoveries of organelle genomes, a new term in the lexicon of somatic cell genetics, “cybrid,” signaled the arrival of a powerful new experimental approach (5). This technique remains a central tool for the investigation of mtDNA mutations in mitochondrial biogenesis and disease 30 years later.