Increased steady-state levels of several mitochondrial and nuclear gene transcripts in rat hepatoma with a low content of mitochondria


Correspondence toŠ. Kužela, Institute of Molecular Biology, Slovak Academy of Sciences, Dúbravská cesta 9, CS-842 51, Bratislava, Czechoslovakia


Cells from a rapidly growing rat Zajdela hepatoma were shown to contain (on a protein basis) five-times less mitochondria than hepatocytes from resting or regenerating rat liver. Transcripts of four nuclear genes for representative mitochondrial membrane proteins (β-F1 subunit and N,N′-dicyclohexyl-carbodimide-binding protein of ATP synthase, subunit IV of cytochrome oxidase and ADP/ATP translocase) were present in 2–4-times higher amounts in the poly(A)-rich RNA of the hepatoma than in the corresponding RNA fraction from resting or regenerating rat liver. The liver and hepatoma transcripts for the β-F1, subunit were translated in an in-vitro system with equal efficiency. Pulse-chase labeling of isolated Zajdela hepatoma cells and hepatocytes from resting and regenerating liver revealed a relative excess of the newly synthesized β-F1 subunit in the tumor cells. The half-life of the β-F1, subunit was significantly shorter in the hepatoma cells than in hepatocytes from resting and regenerating liver. The contents of transcripts of three mitochondrial genes examined (cytochrome oxidase subunits I and II and NADH-ubiquinone reductase subunit 2) in Zajdela hepatoma mitochondria were about five-times higher than in the mitochondria of the resting cells and 3–4 times higher than in the organelles of the regenerating organ. The results indicate that events other than transcription (most likely post-translational) may be responsible for the reduced content of mitochondria in tumor cells.


β subunit of the F1-ATPase