Cell Death - Mechanisms of Apoptosis, Necrosis, and Autophagy

A set of 50 comprehensive vocabulary flashcards covering the types, characteristics, molecular regulators, and signaling pathways of cell death based on Dr. Alakananda Basu's lecture.

Apoptosis

A genetically programmed, physiologic form of cell death (derived from the Greek for "away from" and "to drop off") essential for tissue homeostasis, development, and defense.

Necrosis

A pathologic or accidental form of cell death (derived from the Greek for "deadness") in which cells swell and burst, releasing intracellular contents and eliciting an inflammatory response.

Autophagy

A cellular survival process of self-cannibalism wherein a cell sequesters and digests its own components in lysosomes to recycle nutrients during starvation; excessive autophagy can lead to cell death.

Programmed Cell Death (PCD)

Genetically encoded cell suicide mechanisms, primarily exemplified by apoptosis, that regulate cell numbers and eliminate redundant, damaged, or infected cells.

Chromatin Condensation

A major morphological hallmark of apoptosis involving the compaction and margination of nuclear chromatin against the nuclear envelope.

Cytoplasmic Blebbing

A characteristic morphological alteration during apoptosis characterized by irregular bulges and protrusions of the plasma membrane prior to cellular fragmentation.

Apoptotic Bodies

Membrane-bound cellular fragments containing condensed cytoplasm and organelles that break off during apoptosis to be engulfed by phagocytes.

Cell Shrinkage

A morphological feature of apoptosis where the cell condenses and decreases in volume without losing plasma membrane integrity or leaking contents.

Internucleosomal DNA Fragmentation

The cleavage of genomic DNA into regular fragments of multiples of $180\,\text{bp}$ during apoptosis, resulting from endonuclease activation.

Phosphatidylserine (PS) Translocation

The loss of plasma membrane asymmetry during apoptosis, marked by the flipping of phosphatidylserine from the inner leaflet to the outer leaflet of the plasma membrane.

"Eat-Me" Signal

The surface display of translocated phosphatidylserine on apoptotic cells that allows recognition and engulfment by phagocytic cells without causing inflammation.

CAD (Caspase-Activated DNase)

An endonuclease responsible for cleaving genomic DNA into internucleosomal fragments during apoptosis once liberated from its inhibitor.

ICAD (Inhibitor of CAD)

The regulatory inhibitor protein that binds and sequesters CAD in viable cells; executioner caspase cleavage of ICAD unleashes active CAD.

Caspases

A family of cysteine proteases (cysteine aspartases) that specifically cleave substrate proteins after aspartate (Asp) residues.

Initiator Caspases

Apical caspases (such as caspases 8, 9, and 10) that contain long pro-domains and are activated by adaptor-mediated oligomerization and protein-protein interactions.

Executioner (Effector) Caspases

Downstream caspases (such as caspases 3, 6, and 7) that contain short pro-domains and are proteolytically activated by initiator caspases to execute cell disassembly.

Procaspase Structure

The inactive zymogen precursor form of a caspase, typically composed of three domains: an $\text{NH}_2$-terminal prodomain, a large subunit, and a small subunit.

Death Effector Domain (DED)

A specialized protein interaction module located within the long prodomain of procaspase-8 and adaptor proteins like FADD.

Caspase Recruitment Domain (CARD)

An amino-terminal protein-protein interaction domain found in procaspase-9 and Apaf-1 that mediates homophilic binding during apoptosome assembly.

Active Caspase Tetramer

The enzymatically active quaternary structure of a caspase formed by the association of two heterodimers (each composed of a cleaved large and small subunit).

CED-9

The C. elegans anti-apoptotic regulatory protein that inhibits the adaptor CED-4; functional homolog of vertebrate Bcl-2.

CED-4

The C. elegans adaptor protein that activates the effector caspase CED-3; vertebrate homolog of Apaf-1.

CED-3

The C. elegans effector caspase whose proteolytic activity executes programmed cell death; homologous to vertebrate executioner caspases like caspase-3.

Bcl-2

The founding member of an apoptosis-regulatory protein family, first identified in B-cell lymphoma, that acts as a mammalian regulatory protein to inhibit cell suicide.

Anti-Apoptotic Bcl-2 Family Members

Pro-survival proteins—such as Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1—that contain four BH domains (BH1–BH4) and maintain mitochondrial outer membrane integrity.

Pro-Apoptotic Effector Bcl-2 Family Proteins

Multi-domain proteins (Bax, Bak, Bok) containing BH1–BH3 domains that form pore channels in the outer mitochondrial membrane upon activation.

BH3-Only Proteins

Pro-apoptotic regulatory members of the Bcl-2 family (e.g., Bim, Puma, Noxa, Bik, Bmf, Bad, Hrk, Bid) that share only the BH3 domain and inhibit anti-apoptotic Bcl-2 members.

Bcl-2 Homology (BH) Domains

Conserved sequence regions (designated BH1, BH2, BH3, and BH4) that govern protein interactions and pore-forming activity among Bcl-2 family members.

Transmembrane (TM) Domain of Bcl-2 Proteins

A hydrophobic segment located at the carboxyl terminus of many Bcl-2 family proteins that anchors them to the mitochondrial outer membrane.

Mitochondrial Integrity

The physical intactness of the outer mitochondrial membrane preserved by anti-apoptotic Bcl-2 family proteins to prevent cytosolic leakage of pro-apoptotic factors.

Cytochrome c

A mitochondrial intermembrane space protein that, upon release into the cytoplasm via Bax/Bak channels, binds Apaf-1 to trigger the intrinsic apoptotic pathway.

Apaf-1 (Apoptotic Protease Activating Factor-1)

A cytosolic adaptor protein that binds cytochrome c in the presence of ATP or dATP to assemble into the heptameric apoptosome complex.

Apoptosome

A wheel-like protein complex assembled from cytochrome c and Apaf-1 that recruits and activates procaspase-9 via CARD-CARD interactions.

Procaspase-9

The initiator caspase zymogen of the intrinsic pathway containing an amino-terminal CARD domain that is recruited to and activated within the apoptosome.

Caspase-9

The active initiator protease of the mitochondrial/intrinsic pathway that cleaves and activates downstream executioner caspases like procaspase-3 and -7.

Procaspase-3

The inactive zymogen form of caspase-3, activated via proteolytic cleavage by initiator caspases such as caspase-9 or caspase-8.

Caspase-3

The primary executioner caspase responsible for cleaving vital cellular substrates, including ICAD, to orchestrate the demise of the cell.

Intrinsic Cell Death Pathway

The mitochondrial cell death pathway triggered by intracellular physiological and pathological stimuli, leading to mitochondrial permeabilization, cytochrome c release, and caspase-9 activation.

Extrinsic Cell Death Pathway

The receptor-initiated cell death pathway activated by extracellular signals when transmembrane death ligands bind corresponding surface death receptors.

Death Receptors

Transmembrane receptors (such as Fas/CD95 and TNF$\alpha$ receptor) possessing an intracellular death domain (DD) capable of initiating extrinsic apoptosis.

Death Domain (DD)

A conserved intracellular protein interaction domain found on death receptors and cytoplasmic adaptor proteins such as FADD and TRADD.

Fas Receptor (CD95)

A cell-surface death receptor that oligomerizes upon binding its trimeric ligand, recruiting adaptor proteins via homotypic death domain interactions.

Fas Ligand (FasL / CD95L)

A death-inducing ligand presented by killer lymphocytes that binds to Fas receptors on target cells to initiate extrinsic apoptotic signaling.

FADD (Fas-Associated Death Domain)

An adaptor protein containing both a death domain (DD) and a death effector domain (DED) that couples clustered Fas receptors to procaspase-8.

TRADD (TNFR-Associated Death Domain)

A cytoplasmic adaptor protein recruited to the death domain of activated TNF$\alpha$ receptors during receptor-mediated apoptosis.

DISC (Death-Inducing Signaling Complex)

A multiprotein plasma membrane complex comprising oligomerized death receptors, FADD adaptors, and procaspase-8 that triggers caspase-8 autoproteolytic activation.

Procaspase-8

The initiator caspase precursor of the extrinsic pathway containing two death effector domains (DEDs) in its prodomain that mediate recruitment to DISC.

Caspase-8

The active initiator protease of the extrinsic pathway that proteolytically activates downstream executioner caspases and cleaves the BH3-only protein Bid.

Bid

A pro-apoptotic BH3-only Bcl-2 family protein that is cleaved by active caspase-8, mediating functional cross-talk between the extrinsic and intrinsic pathways.

tBid (Truncated Bid)

The active cleaved product of Bid produced by caspase-8 that translocates to the mitochondria to induce Bax/Bak pore formation and cytochrome c release.