From the Guidelines
Cells can die through two main regulated processes: apoptosis and autophagy, with apoptosis being a form of programmed cell death and autophagy being a survival mechanism that can lead to cell death when excessive, as supported by recent studies 1. The mechanisms of cell death are complex and involve multiple pathways. Apoptosis is characterized by cell shrinkage, nuclear fragmentation, chromatin condensation, and membrane blebbing, ultimately resulting in the formation of apoptotic bodies that are engulfed by phagocytes without triggering inflammation. This process is controlled by caspase enzymes and can be initiated through either the intrinsic pathway (triggered by internal cell damage, involving mitochondrial release of cytochrome c) or the extrinsic pathway (activated by death receptors on the cell surface) 1. Autophagy, on the other hand, is primarily a survival mechanism where cells digest their own components in response to stress or nutrient deprivation, but can lead to cell death when excessive. During autophagy, cellular components are enclosed in double-membrane vesicles called autophagosomes, which then fuse with lysosomes for degradation and recycling of the contents. Some key points to consider when evaluating cell death mechanisms include:
- The relationship between autophagy and cell death remains controversial, with some studies suggesting that autophagy can have both promoting and protective effects on cell death 1
- The correct classification of cell death into specific subroutines is crucial for its therapeutic implications, as different cell death modes (e.g., apoptosis, necrosis) may have different responses to therapeutic interventions 1
- The use of standardized guidelines for detecting and interpreting cell death is essential for ensuring consistency and accuracy in experimental approaches 1 In summary, apoptosis and autophagy are two distinct mechanisms of cell death, with apoptosis being a programmed process and autophagy being a survival mechanism that can lead to cell death when excessive, and the correct understanding and classification of these mechanisms is crucial for developing effective therapeutic strategies, as highlighted in recent studies 1.
From the Research
Mechanisms of Cell Death
The mechanisms of cell death, including apoptosis and autophagy, are complex and interconnected processes that regulate cell survival and death under stress conditions 2, 3, 4, 5, 6.
- Apoptosis is a process that aims to remove damaged or unwanted cells from the body with minimal damage to surrounding tissues 2, 4.
- Autophagy, on the other hand, promotes the removal of damaged organelles, protein aggregates, and cellular pathogens, stimulating cell survival 2, 3, 4, 5, 6.
- The signaling pathways involved in the regulation of apoptosis and autophagy largely overlap, leading to both competition and unidirectional interaction 2, 3, 6.
Signaling Pathways and Molecular Interactions
The signaling pathways involved in apoptosis and autophagy are regulated by various molecular interactions, including:
- Mitochondrial dysfunction, oxidative stress, calcium ion concentration, reactive oxygen species, and endoplasmic reticulum stress 3.
- Key signaling molecules such as p53 and VEGF, which mediate angiogenic pathways and trigger apoptotic and autophagic pathways 3.
- The involvement of signaling molecules such as mTOR, Bcl-2, BH3 family members, caspases, AMPK, PI3K/Akt/GSK3β, and p38/JNK/MAPK in the pathogenesis and progression of neurodegenerative diseases 3.
Autophagy and Apoptosis Cascade
The autophagy and apoptosis cascade is a complex process that determines the fate of cellular organelles and proteins involved in human health and disease 3, 6.
- Autophagy can lead to cell death, and the same stresses can stimulate both autophagy and apoptosis 4, 5.
- The molecular connections between autophagy and cell death are complicated, and autophagy may promote or inhibit cell death in different contexts 5.
- The discovery of Beclin-1's interacting partners has resulted in the identification of Bcl-2 as a central regulator of autophagy and apoptosis 6.