Cell Death

Cell death is a core biological process for maintaining organismal homeostasis. Cell death can be divided into two categories: nonregulated (accidental) cell death and regulated cell death. Nonregulated cell death is passively triggered by external factors such as physical and chemical damage and does not involve intracellular signaling pathways and execution mechanisms. Regulated cell death is an ordered process. Genetically encoded, orchestrated and tightly regulated regulated cell death serves as a more promising target for therapeutic intervention. It acts as a vital mechanism for tissue sculpting, sustaining homeostasis, and enabling host defense against tumors and pathogenic invasion. Regulated cell death has two subtypes. One subtype is triggered by overload or depletion of nutrients (e.g., glucose and amino acids) or metal ions (e.g., iron and copper), ultimately leading to cellular metabolic imbalance. This form of cell death is defined as metabolic cell death and is often referred to as "cell sabotage". The other subtype is "cell suicide", which is directly initiated by signaling cascades and cell death executioner proteins to eliminate redundant cells in organisms.

1 "Cell sabotage" — Metabolic Cell Death

In-depth analysis of metabolic cell death helps elucidate the rules of disease progression, facilitates the development of innovative therapeutic strategies for various diseases (especially cancers), and provides new ideas to overcome drug resistance to conventional therapies. Metabolic cell death includes:

1. Ferroptosis
2. Cuproptosis
3. Disulfidptosis
4. Lysozincrosis
5. Alkaliptosis
6. Calcicoptosis
7. Necrosis by Sodium Overload
8. Manganoptosis
9. Cobaltoptosis

2 “Cell suicide” — cell death initiated by signaling cascades and direct activation of cell death execution proteins

Cell suicide refers to a process in which cells actively initiate and execute their own elimination through highly regulated molecular programs in response to specific endogenous or exogenous signals. This process is typically mediated by the sequential activation of a series of proteases, kinases, or effector proteins through signaling cascades. Cell suicide represents an essential mechanism for maintaining organismal development, tissue homeostasis, and immune system balance in multicellular organisms. It includes:

1. Apoptosis
2. Necroptosis
3. Pyroptosis
4. Autophagy-dependent cell death
5. PARP-dependent cell death (Parthanatos)
6. Lysosome-dependent cell death
7. Mitochondrial permeability transition (MPT)-mediated cell death