Connecting the Dots Between Inflammation and the Inner Workings of Programmed Cell Death

Programmed cell death (PCD) is central in maintaining the life of multicellular organisms, during development as well as in healthy adulthood or in the context of disease. The best understood form of PCD is apoptosis, a caspase mediated, immunologically silent cell death that can be initiated in probably all cell types upon aging, lack of growth support, critical damage or infection. One of the key pathways of apoptosis involves mitochondrial outer membrane permeabilization (MOMP), a process tightly regulated by members of the BCL-2 family. Whereas PCD and apoptosis were used synonymously in the past, other forms of PCD have been discovered more recently, including RIPK1/3- and MLKL-dependent necroptosis, resulting in a necrotic phenotype, and pyroptosis. Interestingly, key components of the necroptotic pathway are actively suppressed by apoptotic caspases, and this interconnection allows a switch in cell death modalities with greatly impact on the host’s immune response. Recent findings link mitochondria and/or MOMP to non-apoptotic forms of PCD, including ferroptosis and necroptosis, putting this organelle even more in the center of cellular death. This article collection highlights the exciting potential and as yet undiscovered regulation of programmed cell death that can impact the immune system and its response.
Submission is open to articles (research articles, reviews, comments, etc.) on topics covering mechanistic insights into all forms of PCD, with a special focus on (but not restricted to) crosstalk between cell death pathways, mitochondrial involvement therein, classical as well as non-conventional roles of cell death regulators (e.g. BCL-2 family, IAP members, RIPK1/3), caspases and cell death activated immune responses. We also encourage submissions of robust observations with minimal mechanistic insight to be submitted as Brief Research Reports.