Also, the expression of the circulating cytokines fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF15), found upregulated in various mitochondrial disease models [46, 47], was significantly induced in PolɣD1135A cells (Fig. 6A; Table S1). Here, FGF21 is linked to inborn mitochondrial metabolism disorder.