For example, mtDNA depletion in HEK293 cells caused by loss of POLG leads to collapse of the TCA cycle and increased serine synthesis [22, 48, 49], and a mouse model of mitochondrial myopathy caused by a defective mtDNA helicase leads to major metabolic disturbances including elevated serine synthesis and disturbed one-carbon metabolism [20]. The gene discussed is POLG; the disease is Mitochondrial myopathy.