Apoptosis (intrinsic/extrinsic), caspases, Bcl-2, necroptosis, pyroptosis, ferroptosis, autophagy, senescence.
Cell Fate Apoptosis Senescence
Apoptosis
Regulated, non-inflammatory cell-death programme: chromatin condensation, membrane blebbing, DNA fragmentation, apoptotic-body formation,…
Caspase
Cys-Asp-specific proteases that execute apoptosis. Initiators (CASP8, 9, 10) cleave + activate effectors (CASP3, 6, 7) that cleave >500…
Intrinsic (mitochondrial) apoptosis
Triggered by intracellular stress (DNA damage, ER stress). BH3-only proteins (PUMA, BIM) activate BAX/BAK → MOMP → cytochrome-c release →…
Extrinsic (death-receptor) apoptosis
Triggered by death ligands (FasL, TNF, TRAIL) binding death receptors → DISC assembly (FADD + procaspase-8) → CASP8 cleaves effector…
Bcl-2 family
Regulators of mitochondrial outer-membrane permeabilisation (MOMP). Anti-apoptotic (Bcl-2, Bcl-xL, Mcl-1); effector (BAX, BAK); BH3-only…
Necroptosis
Regulated necrotic-like death via RIPK1-RIPK3-MLKL axis. MLKL oligomerises, translocates to plasma membrane, permeabilises → cell rupture +…
Pyroptosis
Inflammatory caspase-1/4/5/11-dependent cell death: inflammasome assembly → gasdermin D cleavage → GSDMD N-terminal pore formation in…
Ferroptosis
Iron-dependent lipid-peroxidation cell death. Suppressed by GPX4 (selenoprotein) reducing lipid peroxides. Targeting GPX4 or cystine import…
Cellular senescence
Stable cell-cycle arrest with altered morphology, SASP (senescence-associated secretory phenotype), persistent DDR. Triggers: telomere…
Anoikis
Apoptosis triggered by loss of ECM attachment; suppresses ectopic cell growth. Resistance to anoikis is a prerequisite for metastasis.
Apoptosis bistable switch (Eissing model)
Caspase-3 activation network (Eissing 2004 / Bagci 2006 ODE) exhibits bistability between live and apoptotic states via positive feedback…
Telomere attrition replicative aging
Hayflick limit emerges from end-replication problem: each S-phase loses Δ ~ 50-100 bp; telomere length L_n = L_0 - n·Δ - σ√n decreases…
Apoptosis (Bcl-2 / Bax / cytochrome-c)
Korsmeyer 1990s Bcl-2 family: Bax/Bak permeabilize mitochondria; cyto-c release -> Apaf-1 apoptosome -> caspase-9 -> caspase-3; Wang 1996…
Caspase cascade (Yuan-Horvitz 1993)
Yuan-Horvitz 1993 ced-3 worm = caspase-1; Nicholson 1995 caspase-3 substrates; initiator + executioner caspases; BIR-domain IAP inhibition;…
p53 tumor suppressor (Vogelstein 1989)
Vogelstein 1989 p53 mutated in >50% cancers; Lane 1979 SV40-large-T binding; transcription factor for cell-cycle arrest (p21) + apoptosis…
Hayflick limit / cellular senescence
Hayflick 1961 50-doubling limit; Harley-Greider-Blackburn telomere-shortening 1990 (Nobel 2009); SASP senescence-associated secretory…
Autophagy (Ohsumi 1992 ATG)
Ohsumi 1992 yeast autophagy genes (Nobel 2016): ATG1-32 protein machinery; LC3 lipidation marks autophagosome; mTOR negative regulation;…
Ferroptosis (Dixon-Stockwell 2012)
Dixon-Stockwell 2012 ferroptosis: iron-dependent lipid-peroxidation programmed cell death; GPX4 master regulator; relevance in…
Intrinsic vs extrinsic
Wajant 2002 intrinsic Bcl-2 + extrinsic Fas/TNFR; modern caspase-cascade + execution-phase + Smac-Diablo.
Necroptosis (Zhang 2009)
Zhang-Han 2009 RIPK1/RIPK3/MLKL programmed-necrosis; modern necroptosis-inhibitor necrostatin + neurodegeneration.
Ferroptosis (Stockwell 2017)
B Stockwell 2017 ferroptosis review; modern GPX4 + lipid-peroxidation + ferrostatin neurodegen + cancer.
Pyroptosis (Shi 2015)
Shi-Zhao-Wang 2015 gasdermin D pore-formation; modern inflammasome + sepsis + IBD + cancer immunotherapy.
Anoikis (Frisch 1994)
S Frisch-H Francis 1994 anoikis ECM-detachment-induced apoptosis; modern circulating-tumor-cell + metastasis-resistance.
SASP (Coppé 2008)
J-P Coppé 2008 senescence-associated-secretory-phenotype; modern senolytics dasatinib+quercetin trial 2019+.