Programmed cell clearance: From nematodes to humans

Programmed cell clearance is a highly regulated physiological process of elimination of dying cells that occurs rapidly and efficiently in healthy organisms. It thus ensures proper development as well as homeostasis. Recent studies have disclosed a considerable degree of conservation of cell clearance pathways between nematodes and higher organisms. The externalization of the anionic phospholipid phosphatidylserine (PS) has emerged as an important "eat-me" signal for phagocytes and its exposition on apoptotic cells is controlled by phospholipid translocases and scramblases. However, there is mounting evidence that PS exposure occurs not only in apoptosis, but may also be actively expressed on the surface of cells undergoing other forms of cell death including necrosis; PS is also expressed on the surface of engulfing cells. Additionally, PS may act as a "save-me" signal during axonal regeneration. Here we discuss mechanisms of PS exposure and its recognition by phagocytes as well as the consequences of PS signaling in nematodes and in mammals. - Highlights: • Cell clearance pathways are conserved between nematodes and mammals. • Phosphatidylserine (PS) externalization is a common signal for cell clearance. • Translocases and scramblases are involved in PS exposure during apoptosis. • PS also functions as a "save-me" signal to mediate the fusion of injured axons. • Definitions of cell death should take into account whether/how cells are cleared.