Saccharopine accumulation induces mitochondrial damage and functional loss in mouse livers. (A and B) TEM images of mitochondria in the livers of WT, Aass(R65Q) (A), and Aass(G489E) (B) mice. Representative mitochondria indicated with numbers are magnified (3×) below each image (WT and Aass(R65Q)) or shown to the right and below (Aass(G489E)). (C and D) The average sizes (C) of mitochondria and the percentage of mitochondria with different sizes (D) in the livers of the indicated mice. ≥400 mitochondria were analyzed for each genotype. (E) ATP levels in the livers of WT, Aass(R65Q), and Aass(G489E) mice. Data (mean ± SEM) are from five mice. (F and G) Dynamics of MitoTracker Green–labeled mitochondria-cultured hepatocytes in WT (F) and Aass(G489E) (G) mice. White and yellow arrows indicate sites of mitochondrial fusion and fission, respectively. Bars, 5 µm. (H and I) OCR in hepatocytes of WT and Aass(R65Q) mice (H) and WT and Aass(G489E) mice (I) under basal conditions and in response to the indicated mitochondrial inhibitors. Data are from four independent experiments. For all quantifications, *, P < 0.05; **, P < 0.01; and ***, P < 0.001. Error bars represent SEM.