Figure 2.

Mitochondrial fragmentation caused by MFN1 knockout or DRP1 overexpression promotes tumorigenesis of c-Myc-driven HB in mice

(A) Representative gross images of livers from MFN1^flox/flox (n = 12) or Alb-Cre; MFN1^flox/flox (n = 12) mice injected with c-Myc/SB plasmids (left panel) or from WT mice injected with c-Myc/pT3 (n = 12) or c-Myc/DRP1 (n = 12) plasmids (right panel). MFN1^flox/flox, MFN1^flox/flox mice hydrodynamically injected with c-Myc plasmid and SB transposon; MFN1 LKO, MFN1 liver-specific knockout mice hydrodynamically injected with c-Myc plasmid and SB transposon; PT3, wild-type mice hydrodynamically injected with c-Myc plasmid and PT3-EF1α empty vector, as well as SB transposon; DRP1, wild-type mice hydrodynamically injected with c-Myc plasmid and PT3-EF1α-DRP1 construct, as well as SB transposon; w.p.i., weeks post-injection. (B and C) Survival curve (B) and liver/body weight ratio (C) of the mice with treatment as indicated. (D) Representative images of hematoxylin and eosin (H&E) and PCNA staining in mouse liver tumors. Scale bar: 50 μm. (E) Percentage of PCNA-positive cells in mouse liver tumors. (F and G) Representative TEM images of mitochondria in mouse liver tumors. Scale bars: 1 μm. Mitochondria and nucleus were pseudo-colored green and blue. The length distribution of mitochondria was analyzed. (H and I) Representative ¹⁸F-FDG micro-PET/CT images and analysis in mice. A higher intensity of red color indicates a higher ¹⁸F-FDG uptake. (J) Lactate production was measured in mouse tumor tissues. ∗p < 0.05, ∗∗p < 0.01.