Animals are profoundly dependent on aerobic ATP generation by mitochondria, and thus the functional properties of this key cellular organelle play an important role in determining organismal performance and fitness in the context of a changing environment. In addition, because of the endosymbiotic origin of the mitochondrion, any adjustments to mitochondrial function necessarily involve tight coordination between both the nuclear and mitochondrial genomes.  Across evolutionary timescales, coadaptation of these interacting gene products is essential for organism function, and differentiation in mitochondrial genes has been suggested to be an important cause of hybrid incompatibility between closely related taxa. In this talk, I will explore some of these issues using examples from my group’s work on the Atlantic killifish (Fundulus heteroclitus).  This species is found in marshes in estuaries along the Atlantic coast from southern Canada to Northern Florida. These habitats are highly variable in temperature, oxygenation level and salinity across tidal and seasonal cycles, and these fish have both high tolerance of variation in these parameters and exhibit substantial phenotypic plasticity. In addition, there is a steep thermal gradient along the Atlantic coast, and killifish populations have undergone local adaptation such that northern and southern populations form genetically distinct groups that differ in thermal tolerance, hypoxia tolerance and metabolic rate. We have examined mitochondrial performance and plasticity in northern and southern killifish and have shown that there are clear differences in mitochondrial performance and oxygen binding capacity. Both populations also exhibit substantial plasticity in mitochondrial function that is associated with changes in mitochondrial membrane lipids.  We also detect evidence of hybrid incompatibility between killifish subspecies, and are currently examining the role of mito-nuclear interactions in this process. Taken together, these data strongly suggest that mitochondrial processes are a major determinant of adaptive variation and plasticity in aerobic performance, thermal tolerance, and hypoxia tolerance in this species.