Abstract
The importance of mitochondria in disease and organismal fitness is well established and recognized, but our current understanding of mitochondrial biology and genetics often struggles to pinpoint mechanisms through which mitochondria exert their influence. Recent findings may radically change our perception of mitochondria’s capacity to have an impact on organismal fitness, revealing the presence of regulatory genetic elements that reside within the mitochondrial genome (mtDNA), but have effects on nuclear gene expression. These elements have remained unnoticed for decades, but their discovery and our growing appreciation for their breadth of impacts on disease and other phenotypes of interest may elevate the mitochondrial genome from bystander to master manipulator.