TK2 and mitochondrial DNA depletion syndrome: Previous studies suggest that the activity of mitochondrial transcription complex is intimately linked to cell metabolism: (1) mitochondrial gene expression is dynamically connected to nutrient supply and bioenergetic requirements (Liesa and Shirihai, 2013; Scarpulla, 2008); (2) genetic mutations of various metabolic enzymes, such as succinate-CoA ligase subunit alpha (SUCLG1), succinate-CoA ligase [ADP-forming] subunit beta (SUCLA2), thymidine kinase 2 (TK2), and deoxyguanosine kinase (DGUOK), are clinically associated with mtDNA depletion syndrome (MDS) (Copeland, 2008).