Navigating the complexities of cell death: Insights into accidental and programmed cell death

Abstract

Cell death is a critical biological phenomenon that can be categorized into accidental cell death (ACD) and programmed cell death (PCD), each exhibiting distinct signaling, mechanistic and morphological characteristics. This paper provides a comprehensive overview of seven types of ACD, including coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous and secondary necrosis, discussing their pathological implications in conditions such as ischemia and inflammation. Additionally, we review eighteen forms of PCD, encompassing autophagy, apoptosis, necroptosis, pyroptosis, paraptosis, ferroptosis, anoikis, entosis, NETosis, eryptosis, parthanatos, mitoptosis, and newly recognized types such as methuosis, autosis, alkaliptosis, oxeiptosis, cuprotosis and erebosis. The implications of these cell death modalities for cellular processes, development, and disease—particularly in the context of neoplastic and neurodegenerative disorders—are also covered. Furthermore, we explore the crosstalk between various forms of PCD, emphasizing how apoptotic mechanisms can influence pathways like necroptosis and pyroptosis. Understanding this interplay is crucial for elucidating cellular responses to stress, as well as for its potential relevance in clinical applications and therapeutic strategies. Future research should focus on clarifying the molecular mechanisms that govern different forms of PCD and their interactions.