Cell death pathways- Dr.M.Jothimuniyandi

Cell death pathways - Dr.Jothimuniyandi -Apoptosis -
Pyroptosis - Necroptosis -
Autophagy

1. Dr.M.Jothimuniyandi Assistant Professor Cell death pathways

2. Cell death pathways play crucial roles in development, ensuring proper formation of tissues, organs, and the elimination of unnecessary or damaged cells. Their dysregulation can lead to a number of pathologies. Some of the major cell death pathways include: Cell death pathways in development

3. Apoptosis A non-lytic type of programmed cell death that results in the formation of apoptotic bodies from the plasma membrane. Pyroptosis A lytic type of programmed cell death that forms pores in the plasma membrane. Necroptosis A lytic type of programmed cell death that forms pores in the plasma membrane. Autophagy An alternative death pathway that may contribute to cell elimination during development. Cell death pathways

4. There are three major types of morphologically distinct cell death: apoptosis (type I cell death), autophagic cell death (type II), and necrosis (type III). All three can be executed through distinct, and sometimes overlapping, signaling pathways that are engaged in response to specific stimuli. Cell death pathways

5. Apoptosis is a well-regulated process crucial for eliminating unnecessary or damaged cells during development. It has two main pathways: a. Intrinsic Pathway (Mitochondrial Pathway): Trigger: This pathway is activated by internal stress signals such as DNA damage, oxidative stress, or lack of growth factors. Key Players: Mitochondria: Release cytochrome c in response to stress. Bcl-2 family proteins: These regulate mitochondrial outer membrane permeabilization . Pro-apoptotic members like Bax and Bak promote cytochrome c release, while anti-apoptotic members like Bcl-2 inhibit it. 1. Apoptotic Pathways (Programmed Cell Death)

6. Apoptosome formation: Cytochrome c binds with Apaf-1 (apoptotic protease-activating factor 1) and procaspase-9, forming the apoptosome , which activates caspase-9. Caspase cascade: Caspase-9 activates downstream executioner caspases (caspase-3, -6, -7), leading to cell death. Role in Development: Involved in shaping organs, such as the nervous system by eliminating excess neurons, and in removing harmful cells like those with damaged DNA. Apoptosis (Programmed Cell Death)

7. b. Extrinsic Pathway (Death Receptor Pathway): Trigger: Initiated by extracellular signals, often involving ligands binding to death receptors on the cell surface. Key Players: Death receptors: Fas (CD95) and Tumor Necrosis Factor Receptor (TNFR) bind ligands like FasL or TNF. DISC formation: Binding activates the death-inducing signaling complex (DISC), which recruits and activates caspase-8. Apoptosis (Programmed Cell Death)

8. Caspase cascade: Activated caspase-8 can directly activate executioner caspases or cleave Bid, linking to the intrinsic pathway by promoting mitochondrial cytochrome c release. Role in Development: Important in immune system regulation, such as the elimination of autoreactive lymphocytes. Apoptosis (Programmed Cell Death)

9. Apoptotic Pathways Source: https://www.assaygenie.com/apoptosis-intrinsic-extrinsic-cell-death-pathways

10. Autophagy is primarily a survival mechanism but can also result in cell death under certain conditions during development. It involves the degradation and recycling of cellular components via lysosomes. Mechanism of Autophagy: Trigger: Activated by nutrient deprivation, hypoxia, or stress, but also during normal developmental processes. Key Players: Autophagosomes : Formed when cytoplasmic components are sequestered in double- membraned vesicles. LC3 (microtubule-associated protein 1A/1B-light chain 3): Plays a crucial role in autophagosome membrane formation. Lysosomal fusion: The autophagosomes fuse with lysosomes to degrade their contents. 2. Autophagic Pathway

11. Regulation: mTOR (mammalian target of rapamycin ) negatively regulates autophagy, while AMPK (AMP-activated protein kinase) promotes it during low-energy states. Role in Development: Autophagy is involved in tissue remodeling , removal of damaged organelles, and in survival under stressful conditions, such as during nutrient scarcity in embryonic development. 2. Autophagic Pathway

12. Autophagic Pathway Source: https://www.researchgate.net/publication/276331145_Autophagy_in_Redox_Signalling/figures?lo=1

13. In some cases, apoptosis and autophagy interact: Apoptosis and Autophagy: If autophagy fails, apoptosis can be activated as a backup. Conversely, autophagy can help delay apoptosis by recycling cellular components during stress. Caspase-8 in Autophagy: Caspase-8, while central to apoptosis in the extrinsic pathway, can also regulate autophagic processes. 3. Cross-talk Between Pathways:

14. While not a form of programmed cell death, necrosis can occur due to injury or trauma. It is less common in normal development but may result from pathological conditions. Developmental Examples: Digit formation: Apoptosis removes the cells between the fingers and toes in the embryo, allowing proper limb formation. Brain development: Apoptosis eliminates excess neurons, refining the brain’s neural connections. Inner ear formation: Apoptosis helps in shaping the cochlea, which is responsible for hearing. 4. Necrosis (Uncontrolled Cell Death):

15. Necrosis Source: https://upload.wikimedia.org/wikipedia/commons/6/69/Structural_changes_of_cells_undergoing_necrosis_or_apoptosis.png

16. QUESTIONS? THANK YOU