Apaf-1: Regulation and function in cell death

Abstract

Apoptosis, a form of programmed cell death, is responsible for eliminating damaged or unnecessary cells in multicellular organisms. Various types of intracellular stress trigger apoptosis by induction of cytochrome c release from mitochondria into the cytosol. Apoptotic protease activating factor-1 (Apaf-1) is a key molecule in the intrinsic or mitochondrial pathway of apoptosis, which oligomerizes in response to cytochrome c release and forms a large complex known as apoptosome. Procaspase-9, an initiator caspase in the mitochondrial pathway, is recruited and activated by the apoptosome leading to downstream caspase-3 processing. Various cellular proteins and small molecules can modulate apoptosome formation and function directly or indirectly. Despite recent progress in understanding the mitochondrial pathway of apoptosis, numerous questions such as the molecular mechanism of Apaf-1 oligomerization and caspase-9 activation remain poorly understood. In addition, reports have emerged showing non-apoptotic functions for Apaf-1. The current review summarizes the latest findings regarding structure-function relationship of Apaf-1 as well as its modifiers.

Keywords: Apaf-1; Apoptosis; Apoptosome; Caspase-9.