Figure 1. Lack of Hspd1 Causes Acute Liver Damage, Hepatic Proliferation, and Cholangiocellular Tumorigenesis.

(A) Electron microscopy and 8-OHdG staining of WT and Hspd1^ΔLPC livers. Arrowhead indicates a classic mitophagosome. Scale bars, 0.5 μm (upper), 50 μm (lower).

(B) Six- and 8-week-old Hspd1^ΔLPC mice and WT littermates.

(C) Survival curve of Hspd1^ΔLPC and WT mice.

(D) Eight-week-old Hspd1^ΔLPC and WT littermate livers. Scale bar, 5 mm.

(E) Serum from 8-week-old Hspd1^ΔLPC mice and WT littermates. Scale bar, 1 cm.

(F) Upper: Ki67 staining of 6-week-old Hspd1^ΔLPC and WT livers. Black arrowheads, Ki67⁺ cholangiocytes; white arrowheads, Ki67⁺ hepatocytes. Lower: double staining of Hspd1 (red) and Ki67 (brown) of 8-week-old Hspd1^ΔLPC and WT livers, indicating foci of hepatocyte (white arrowhead) and cholangiocellular (black arrowhead) proliferation. Scale bar, 50 μm.

(G) Quantification of cholangiocellular lesions and Ki67⁺ hepatocytes over time in Hspd1^ΔLPC mice and WT littermates.

(H) H&E staining of Hspd1^ΔLPC liver. Arrowheads indicate biliary intraepithelial neoplasia. Scale bar, 100 μm.

(I) IHC analysis in 8-week-old WT and Hspd1^ΔLPC livers. Scale bar, 50 μm.

(J) Genomic hybridization profiles of CK19⁺ cholangiocellular neoplasia.

(K) Macroscopy (left) and CK19 staining (right) of tumor graft from severe combined immunodeficiency Beige liver. Scale bars, 5 mm (left), 100 μm (right).

(L) Quantification of cholangiocellular lesions over time in AAV8-Cre Hspd1^loxP/loxP and control mice.

(M) H&E and CK19 staining of AAV8-Cre Hspd1^loxP/loxP livers. Scale bar, 100 μm.

Data are represented as the mean ± SEM. *p < 0.05, ***p < 0.001. ns, not significant. See also Figures S1 and S2.