In eukaryotic organisms, nuclear and cytoplasmic genomes interact to drive cellular functions. These genomes have co-evolved to form specific nuclear-cytoplasmic interactions that are essential to the origin, success, and evolution of diploid and polyploid species. Hundreds of genetic diseases in humans and phenotypic variations in plants are known to be the result of alterations affecting nuclear-mitochondrial (NM) communication. The genetic bottleneck in the nuclear genome of modern polyploid wheat species is mirrored by the homogeneity of cytoplasmic genomes in durum and bread wheat cultivars. This lack of variation is illustrated by our data indicating that the mitochondrial genome of durum wheat is almost identical to that of published bread wheat genome. The data by our group and others clearly illustrate that genes affecting NM interactions are directly or indirectly related to hybrid compatibility. Therefore, their manipulation and use would permit wider usage of alien germplasm and more efficient introgression. Thus, we have embarked on a series of studies to: 1) isolate, characterize and manipulate genes involved in NM interaction; 2) better understand the influence of cytoplasmic genome by analyzing the vast collection of wheat alloplasmic lines; and 3) determine the extent of mitochondrial genome variability in Triticeae and Aegilops species in order to generate more cytoplasmically variable, and agronomically adapted cultivars. Utilizing traditional genetic mapping and radiation hybrid mapping, we located a gene in durum wheat (T. turgidum L. var. durum) involved in NM compatibility to a chromosome segment of a few hundred Kb in size. Isolation and characterization of this gene will provide us the ability to understand and manipulate regulatory mechanisms responsible for a number of developmental processes in durum wheat, including embryo/seed development and plant vigor. In parallel, we have demonstrated that variation in the cytoplasmic genome can influence plant-pathogen response such as the interaction with Pyrenophora tritici-repentis (tan spot) and Puccinia triticina (leaf rust). Sequencing the mitochondrial genome of an alloplasmic wheat line indicated a great amount of sequence and structural changes in the genome, and at a much higher frequency than is observed in evolutionarily distant species. Additionally, our data indicated paternal leakage, heteroplasmy and stoichiometric changes in the mitochondrial genomes. These results have important implications in terms of the potential to manipulate plant mitochondrial genomes and select for changes that are critical to plant development and adaptation.