Mitochondrial metabolism decreases in primitive OrthoEs, in line with an increased mitophagy signature. (A-C) Decreased TCA cycle carboxylic acids and amino acids (A) and proteins (B), along with depleted levels of fatty acid oxidation intermediates acylcarnitines (C), are shown. (D) Despite decreases in all mitochondrial enzymes and metabolites, OrthoE cells were characterized by higher levels of mitochondrial fission and antiapoptotic pathways FIS1 and BCL2L1. *P < .05, **P < .01, ***P < .001, ****P < .0001. AU, arbitrary unit; FH, fumarate hydratase; MDH, malate dehydrogenase; NADH, reduced NAD with hydrogen; OGDH, oxoglutarate dehydrogenase; SDHB, succinate dehydrogenase B; SUCLA, succinyl-CoA ligase.