ABSTRACT
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.
