Mitochondria are best known as the sites for production of respiratory ATP and are essential for eukaryotic life. They have their own genome but the great majority of the mitochondrial proteins are encoded by the nuclear genome and are imported into the mitochondria. The mitochondria participate in critical central metabolic pathways and they are fully integrated into the intracellular signalling networks that regulate diverse cellular functions. It is not surprising then that mitochondrial defects or dysregulation have emerged as having key roles in ageing and in the cytopathological mechanisms underlying cancer, neurodegenerative and other diseases. This special issue contains 12 publications—nine review articles and three original research articles. They cover diverse areas of mitochondrial biology and function and how defects in these areas can lead to disease. In addition, the articles in this issue highlight how model organisms have contributed to our understanding of these processes.