Abstract
Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel non-apoptotic forms of RCD have been identified and are increasingly being implicated in various human pathologies. Here, we critically review the current state of the art regarding non-apoptotic types of RCD, including necroptosis, pyroptosis, ferroptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis and oxeiptosis. The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss.
Highlights
The scientific observation of regulated cell death (RCD) historically began in 1842 when Karl Vogt noticed dying cells in toads
RCD occurs through a variety of subroutines that cause cells to be dismantled in different ways, producing distinct morphological changes and immunological consequences
It will be important to assemble a standard panel of biomarkers and functional tests including genetic and pharmacological inhibition studies to accurately distinguish between different forms of RCD that may occur in a “pure” form or in “mixed” variants, in which distinct lethal subroutines come into action in a parallel and sometimes hierarchized fashion
Summary
Daolin Tang[1,2], Rui Kang[2], Tom Vanden Berghe[3,4,5], Peter Vandenabeele 3,4,6 and Guido Kroemer[7,8,9,10,11,12,13]. Cells may die from accidental cell death (ACD) or regulated cell death (RCD). ACD is a biologically uncontrolled process, whereas RCD involves tightly structured signaling cascades and molecularly defined effector mechanisms. A growing number of novel nonapoptotic forms of RCD have been identified and are increasingly being implicated in various human pathologies. We critically review the current state of the art regarding non-apoptotic types of RCD, including necroptosis, pyroptosis, ferroptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis and oxeiptosis. The in-depth comprehension of each of these lethal subroutines and their intercellular consequences may uncover novel therapeutic targets for the avoidance of pathogenic cell loss
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