Journal of Clinical & Experimental Pharmacology

Abstract

Hepatocyte Apoptosis at the Interplay of Intracellular Organelles and Membrane-Bound Receptors: Targets for Therapy

Golnar Karimian, Klaas Nico Faber and Han Moshage

Hepatocyte apoptosis is ubiquitous in liver diseases. Although apoptosis is primarily a non-inflammatory process responsible for removing excess or damaged cells, un-controlled apoptosis can deteriorate organ function. E.g. if apoptotic bodies are not eliminated, their membranes become permeable, leading to the release of cellular fragments into the extracellular space and triggering an inflammatory response, a process called secondary necrosis. In massive liver injury, the ability of phagocytes to identify and clear apoptotic bodies is likely disturbed and an inflammatory response is observed despite an initial apoptotic stimulus in the liver. Therefore, understanding the cellular processes and molecular signaling pathways regulating apoptosis and/or necrosis in hepatocytes is essential to the development of new therapeutic strategies for (chronic) liver diseases. In particular, the intracellular organelles and membrane receptors that are involved in hepatocyte cell death and their interactions are of substantial interest, as a single toxic stimulus often activates several intracellular apoptotic pathways simultaneously. In this review, we discuss recent advances in organelle-mediated and membrane receptor-mediated cell death and potential targets for therapy in hepatocytes.