Altered metabolism by autophagy defection affect liver regeneration

Abstract

Autophagy is the primary intracellular catabolic process for degrading and recycling long-lived proteins and damaged organelles, which maintains cellular homeostasis. Autophagy has key roles in development and differentiation. By using the mouse with liver specific knockout of autophagy related gene 5 (Atg5), a gene essential for autophagy, we investigated the possible role of autophagy in liver regeneration after 70% partial hepatectomy (PHx). Ablation of autophagy significantly impaired mouse liver regeneration, and this impairment was associated with reduced hepatocellular proliferation rate, down-regulated expression of cyclins and tumor suppressors, and increased hepatocellular apoptosis via the intrinsic apoptotic pathway. Ablation of autophagy does not affect IL-6 and TNF-α response after PHx, but the altered hepatic and systemic metabolic responses were observed in these mice, including reduced ATP and hepatic free fatty acid levels in the liver tissue, increased glucose level in the serum. Autophagy is required to promote hepatocellular proliferation by maintaining normal hepatic and systemic metabolism and suppress hepatocellular apoptosis in liver regeneration.