Mitochondria are well recognized to be the key source of ATP generation, thus dubbed the “powerhouse” of the cell. Mitochondria are also important signaling hub, affecting many key cellular processes. We have previously made the fascinating discovery that mild disruption of the electron transport chain results in C. elegans mutants that live longer! Through a targeted RNAi screen, we have identified the homeobox transcription factor CEH-23 to mediate the effects of mild ETC disruption on longevity. Interestingly, CEH-23 is mainly expressed in the neurons. We will be excited to investigate how CEH-23 mediates the longevity effects associated with mild mitochondrial dysfunction.