Welcome to the 0359-684: Cell death; Apoptosis, Necrosis and therapeutic opportunities

1. Basic Cell Biology, major cellular functions: cell division, cellular differentiation and cell death. History of Physiological Vs pathological cell death. Chemistry of life Eukaryotic cells Vs Prokaryotic cells Compartmentalization for better regulations of gene expression and other complex biological reactions Cell structure Cell types Major cellular components: Plasma membrane An asymmetrical Lipid bi-layer Phasphatidylethenolamine, phasphatidylserine, phasphatidylcholine, sphingomylein, membrane proteins, glycolipids, glycoproteins Cholesterol (important for provide structural rigidity to membrane) Membrane proteins: Receptor proteins, ion channels and transport proteins Functions: as barrier between cytoplasm and extra-cellular environment, Controlled transport of chemicals, ions and macromolecules Exocytosis and endocytosis Signal transduction, Generation of action potential

2. Welcome to the 0359-684: Cell death; Apoptosis, Necrosis and therapeutic opportunities

5. Endomembrane system in eukaryotic cells

6. Endoplasmic reticulum: Lipid bilayer forming a continuous sheet enclosing a single space called ER lumen or cisternal space Rough and smooth ER Functions: Protein synthesis Post-translational modification (glycosylation Glycolipd synthesis Vesicular Protein transport and secretion Detoxification (Smooth ER contain cytochrome P450), water insoluble toxic compounds are converted into excretable non-toxic soluble compounds Ca2++ sequestering: Examples- muscle cells (ER is called sarcoplamic reticulum), nerve cells. Golgi bodies: Membrane bound flattened sacs stacked over each other. Functionally distinct parts (cis and trans parts) Contains protein modification enzymes e.g. glycosyl transferase, nucleoside diphosphatase and acid phosphatase Functions: Posttranslational modifications (glycosylation, dephosphorylation, phosphorylation) Involved in sorting and packaging macromolecule for secretion or for delivery to other organelles. Proteins destined for delivery to lysosomes are labelled with mannose-6-phospate in Golgi bodies. Defect in this process results in lysosomes without hydrolytic enzymes and secretion of these enzyme in I-cell disease or inclusion cell disease).

7. Nuclear envelope: Scanning Electron micrograph of nuclear envelope showing nuclear pores.

8. Nucleus and Nuclear envelope: Chromatin Function: Replication, transcription Protein import and RNP export across nuclear envelope

9. Mitochondrial structure Structure of chromatin

10. Lysosomes: Membrane-bound vesicles containing hydrolytic enzymes Function: Involved in intracellular digestion Peroxisomes: Membrane-bound vesicles containing oxidative enzymes such as catalase and urate oxidase, and long chain fatty acid oxidation during which there is production of hydrogen peroxide. Functions: Vestige of an ancient organelle that carried out oxidative reactions May play role in anti-oxidative defence Mitochondria: Double membrane-bound structures, power plants of eukaryotic cells Site for citric acid cycle and oxidative phosphorylation and fatty acid metabolism in energy generating biochemical pathway Outer mitochondrial membrane Inter-membrane space Inner mitochondrial membrane (contains components of electron transport chain, ATP synthase, and transport proteins) Matrix space (contains enzymes and cofactors for citric acid cycle, fatty acid metabolism, mitochondrial genome, and transcription and translation machinery) Inner mitochondrial potential is generated and maintained by proton export out side ATP is synthesis is driven by proton flow towards inside Protein import into mitochondria

11. Secretory cell of pancreas

12. Role of solvent i.e. water and solute in the origin of life

13. Role of solvent i.e. water and solute in the origin of life Importance of lipids in origin of life Membrane formation is thermodynamically favorable process

20. Cellular signalling and cell division • Cellular signalling: • Evolution of social behaviour in cells • Cell to cell communication and responses are essential for the organism as whole. • Different types of cell signalling: • synaptic • Endocrine • Paracrine • Autocrine • Cell to cell signalling by direct contacts: a) via receptors b) via gap junctions and plasmadesmata • Extra-cellular signals: • Hormones • Cytokines • Growth factors • Signalling Mechanisms: • Receptor enzyme mediated • G-protein linked Receptor mediated • Ion-channel-linked Receptor mediated • Intra-cellular Receptor mediated

24. Ion channel-linked Receptors: Neurotransmitter receptors NMDA receptors, serotonin, acetylcholine receptors etc Binding----opening of ion channel------influx of Na, or K or Ca ions----downstream events Drugs: barbiturates, antidepressants used as blockers

26. Receptor enzyme mediated: Receptor tyrosine kinases Examples- receptors for most of growth factors e.g. FGF, PDGF, Insulin, IGF-1, CSF Binding of ligand to RTK----activation of TK activity------autophosphorylation-----binding of GTPase activating protein or PI3 kinase or phospholipase----Activation of PKC and/or Ras---activation of MAPKKK----activation of MAPKK---Activation of MAPK----c-Jun---activation of transcription Receptor serine/threonine kinases: Examples- TGF-b family of receptors