Cell death triad: Integrating apoptotic, autophagic, and necrotic cell death mechanisms

Cell death mechanisms represent fundamental biological processes essential for homeostasis, development, and disease response. Recent advances have expanded our comprehension of these processes and contributed to the identification of novel mechanisms that orchestrate these processes. Apoptosis, a well-characterized form of cell death involving characteristic morphological changes and multiple enzymes that orchestrate the biochemical process, with minimal damage to surrounding cells or tissues and clearing off the apoptotic bodies by phagocytic cells. Dysregulation in the biochemical process could eventually lead to various pathologies including cancer and neurodegenerative disorders. Autophagy primarily a cell survival process that recycles cellular components, can paradoxically contribute to cell death under specific conditions especially when apoptosis is inhibited. Necrosis, once considered purely accidental, is now recognized to include regulated forms such as necroptosis, with defined molecular triggers and execution pathways. In this review, we will explore a general overview of the current comprehension of these major known cell death pathways such as apoptosis, autophagic cell death, necrosis, and necroptosis along with their crosstalk and potential targets in the biochemical mechanisms for therapeutic modulation of these processes that have major clinical implications.