Table 1.
Similarities and differences between apoptosis, necrosis, autophagy, and parthanatos.
| Features | Parthanatos | Apoptosis | Necroptosis | Autophagy |
|---|---|---|---|---|
| Morphological features | Dissipation of the inner transmembrane potential, nuclear and chromatin condensation | Cellular and nuclear volume reduction, chromatin agglutination, nuclear fragmentation, formation of apoptotic bodies and cytoskeletal disintegration, no significant changes in mitochondrial structure | Plasma membrane breakdown, generalized swelling of the cytoplasm and organelles, moderate chromatin condensation, spillage of cellular constituents into the microenvironment | Formation of double-membraned autolysosomes, including macroautophagy, microautophagy and chaperone-mediated autophagy |
| Biochemical features | DNA injury, energy depletion and PAR accumulation | DNA fragmentation | Drop in ATP levels | Increased lysosomal activity |
| Regulatory pathways | PARP1/AIF signaling pathway | Death receptor pathway, mitochondrion pathway and endoplasmic reticulum pathway; caspase, P53, Bcl-2-mediated signaling pathway | Tumor necrosis factor type 1 (TNF-R1) and Receptor-interacting protein 1 (RIP1)/RIP3-mixed-lineage kinase domain-like (MLKL) related signaling pathways; protein kinase C (PKC)-mitogen-activated protein kinase (MAPK)-activatorprotein1 (AP1) related signaling pathway; ROS-related metabolic regulation pathway | Molecular target of rapamycin (mTOR), Beclin-1, P53 signaling pathway |
| Key genetic inhibition or inhibition by protein overexpression | PARP1 knockout, AIF down-regulation (e.g., in Harlequin mouse) |
Bcl-2 overexpression, Inhibition of caspases (3, 8, and 9), Inhibition of PP2Ad, CrmA expression |
Inhibition of RIP1 or RIP3 | Inhibition of Activating molecule in BECN1-regulated autophagy protein 1 (AMBRA1), Recombinant human autophagy related 5/7/12 (ATG5/7/12), or Recombinant Beclin 1 (BECN1) |
| Examples of trigger factors and/or conditions | Excitotoxicity Ischemia Stroke Reactive oxygen/nitrogen species |
Death receptor signaling Dependence receptor signaling DNA damage Trophic factor withdrawal Viral infections |
Excitotoxicity Ischemia Stroke Reactive oxygen/nitrogen species |
Amino acid starvation Serum starvation Protein aggregates |