Mitochondrial dysfunction is an important cause of human disease and is heavily implicated in age-associated diseases and aging (Larsson, 2010). Regulation of mtDNA expression is essential for maintaining cellular energy homeostasis because biogenesis of the oxidative phosphorylation system is critically dependent on key subunits encoded by mtDNA. For more than two decades, MTERF1 has been implicated in regulating transcription termination in mammalian mitochondria, but its molecular mode of action has remained elusive. In a recent breakthrough study published in Cell, the atomic structure of MTERF1-bound mtDNA was solved (Yakubovskaya et al., 2010). Of interest, the MTERF1 protein has a novel fold, unwinds its DNA target, and causes base eversion (Figure 1A), which is critical for transcription termination (Yakubovskaya et al., 2010).