The augmenter of liver regeneration induces mitochondrial gene expression in rat liver and enhances oxidative phosphorylation capacity of liver mitochondria.

Abstract

The mammalian augmenter of liver regeneration gene encodes a protein involved in the unique process of liver regeneration. The augmenter of liver regeneration respective protein stimulates hepatocyte proliferation in hepatectomized rats and inhibits cytotoxic activity of liver-derived Natural Killer cells from intact rats. Augmenter of liver regeneration protein shares homology with a Saccharomyces Cerevisiae protein essential for the viability, oxidative phosphorylation and cell-division cycle. To demonstrate if augmenter of liver regeneration protein, like the homologous in the yeast, plays a role in the regulation of biogenesis of mitochondria. Augmenter of liver regeneration protein was injected in intact rats and, in the hepatic tissue, the expression of two genes located in two different regions of the mitochondrial genome, mitochondrial ATPase 6/8, and ND1 subunit, and of a nuclear gene, mitochondrial Transcription Factor A, were considered. In addition, cytochrome content and oxidative phosphorylation capacity of liver-derived mitochondria were evaluated. The augmenter of liver regeneration protein administration induces an increase in the mitochondrial gene expression and enhances cytochrome content and oxidative phosphorylation capacity of liver-derived mitochondria. The present data demonstrate a comparable role in the regulation of mitochondria biogenesis in the eukaryotic cell like the yeast protein. This phenomenon could be part of the complex mechanism through which augmenter of liver regeneration regulates hepatocyte proliferation.