Increase of mtDNA-Binding Proteins and Mitochondrial mRNAs in Regenerating Liver

Abstract

In order to elucidate the mechanism of energy supply for liver regeneration after partial hepatectomy, we investigated mtDNA replication and transcription in regenerating rat liver. Changes of mtDNA-binding proteins, mtDNA, and mitochondrial mRNAs were monitored at 0, 12, 24, 48, 96, and 168 hr after the operation by gel mobility shift assay and Southern and Northern blot analyses, respectively. We focused on mtDNA-binding proteins specific for four different sequence elements possibly involved in regulation of mtDNA replication and transcription. Amounts of all the proteins sharply increased to maximum (4- to 10-fold of the preoperative level) 12 hr after partial hepatectomy and then decreased for 24 hr. After 24 hr, the amount of the respective binding protein changed diversely. Mitochondrial mRNA levels per gram tissue weight were unchanged during the first 12 hr after partial hepatectomy, but dramatically increased to maximum (4-fold) at 24 hr. In contrast, mtDNA content, expressed as a ratio of the nuclear cytochromec1gene, was unchanged during the first 48 hr and then started to increase, reaching maximum (1.5-fold) at 4 days. These results suggest that the energy supply in the early stage of the liver regeneration following hepatectomy is achieved mainly through enhancement of mtDNA transcription in which the mtDNA-binding proteins probably play regulatory roles.