1. CHAPTER 6 SYSTEMS BIOLOGY OF CELL ORGANIZATION
Prepared by
Brenda Leady, University of Toledo

2. Systems biology
Researchers study living organisms in terms of their underlying network structure rather than their individual molecular components
The goal is to understand how the organization of the cell arises by complex interactions between its various components and parts

3. All modern cells come from preexisting cell by division
All cells posses a genome
Living cells require pre-existing molecules
Cells require pre-existing organization

4. Cell’s genetic information produces proteome
Information in most genes is used to make mRNA molecules that encode amino acid sequences of proteins
Study of individual proteins does not provide a broad integrated look at the dynamic nature of the cell

5. Genomes, proteomes and cell structure function and organization
The proteome is largely responsible for the structure and function of living cells
Gene and protein regulation causes the proteome to be dynamic
Proteins have sorting signals

7. Proteins often undergo protein-protein interactions
Cells must continually synthesize new molecules and break down unwanted components

9. Molecular machines
A machine is an object that has moving parts and does useful work
These machines provide structure and organization to cells and enable them to carry out complicated processes
ATP synthase is a molecular machine that makes ATP
Molecular recognition allows for complex assembly
Subunits recognize each other and bind in a specific way

11. Other molecular machines

12. Cytoskeleton
Key role in cell organization and many processes that maintain the cell
Provides mechanical strength, cell shape, organization and direction to intracellular and cellular movements

15. Molecular recycling Large molecules, except DNA, have finite lifetimes
Half-life varies from 5 minutes for mRNA in prokaryotes to 30 minutes to several days for mRNA in eukaryotes
Continual degradation of faulty or nonfunctional proteins and synthesis of new ones

16. Proteasome Molecular machine for protein degradation
4 stacked rings with caps in eukaryotes
Ubiquitin directs unwanted proteins to proteasomes in eukaryotes
Proteases degrade the unwanted protein into peptides and amino acids

18. Four systems work together
Interior of the nucleus
Cytosol
Endomembrane system
Semiautonomous organelles
Play a role in their own structure and in the structure and organization of the entire cell

20. Nucleus
Genome produces the proteome that is responsible for the structure and function of the entire cell
Gene regulation important in creating specific cell types and enabling response to environmental change
Nucleus organizes itself with the nuclear matrix
Collection of filamentous proteins

21. Cytosol Important coordination center
Compartment for metabolism- synthesis and breakdown
Cytoskeleton found here

22. Endomembrane system
Secretory pathway to move substances in and out of the cell
Secretory and endocytic pathways
Membranes are dynamic and change over time
Nuclear membrane during cell division
Lipids and proteins made and sorted
Storage and recycling
Vacuoles and lysosomes

23. Semiautonomous organelles
Tend to be independent
Mitochondria make ATP
Crucial for cell organization
Chloroplasts capture light to store energy for later use

24. Endomembrane system
Golgi apparatus, lysosomes, vacuoles, secretory vesicles, and plasma membrane
Reside in cytosol
Much of its activity related to transport between compartments
Critical for lipid synthesis, protein synthesis and sorting, and the attachment of carbohydrates to lipids and proteins

25. Lipid synthesis
Cytosol and endomembrane system work together to synthesize most lipids
Building blocks of phospholipids made by enzymes in the cytosol or from the diet
Phospholipids initially made in cytosolic leaflet but flipases in ER membrane transfer some to the other leaflet

27. Lipid transfer
Lipids made in the ER membrane can be transferred to other membranes by…
Lateral diffusion
Vesicle transport
Lipid exchange proteins

29. Studied pancreatic cells secreting proteins
Palade demonstrated that secreted proteins move sequentially through organelles of the endomembrane system
Thousands of different proteins must be sorted to the correct locations
George Palade’s team used pulse-chase experiments to determine where radioactive proteins were produced and the pathways they took
Studied pancreatic cells secreting proteins
Followed radioactive proteins from synthesis in the rough ER and movements through cellular compartments

31. Protein localization
Sorting signals or traffic signals are short amino acid sequences that direct protein to correct cellular location
Most eukaryotic proteins begin synthesis (translation) on ribosomes in the cytosol

32. Proteins that stay in the cytosol lack sorting signals so they stay in the cytosol
Proteins for the nucleus, mitochondria, chloroplasts, and peroxisomes occur after the protein is made
Post-translational sorting
Synthesis of other proteins destined for ER, Golgi, lysosome, vacuole, plasma membrane, or secretion halts until the ribosome is bound to the ER
Cotranslational sorting

34. Proteins that stay in the ER have ER retention signals
Other proteins must be sorted
Transported by vesicles
Vesicles incorporate coat proteins
Also incorporates v-snare indicative of cargo
T-snare on target recognizes v-snare and vesicle fuses with target membrane

36. Glycosylation Attachment of a carbohydrate to a protein
Glycoprotein
May aid in protein folding, extracellular protection, and protein sorting

37. 2 forms of glycosylation
N-linked
Carbohydrate attaches to nitrogen atom of asparagine in polypeptide chain in ER lumen
Occurs in cell membrane surface proteins
Role in cell-to-cell signaling
O-linked
String of sugars attaches to oxygen of serine or threonine in polypeptide
Occurs only in the Golgi apparatus
Important in extracellular matrix proteins

39. Semiautonomous organelles
Semiautonomous because they divide by fission to produce more of themselves
Somewhat independent
Genetic material, synthesize some proteins, divide independently of cell
Do depend on the cell for raw materials and most of their proteins

40. Mitochondria and chloroplasts
2 traits similar to bacteria
Contain DNA separate from the nuclear genome
Mitochondrial and chloroplast genome
Single small circular double stranded chromosome
Similar to bacterial chromosomes
Reproduce via binary fission
Like bacteria

42. Genes of mitochondria and chloroplasts very similar to bacterial genes
Mitochondria and chloroplasts are derived from ancient symbiotic relationships
Endosymbiosis- a smaller species lives symbiotically inside a larger species
Beneficial for both species
Genes of mitochondria and chloroplasts very similar to bacterial genes
Endosymbiosis theory
Modern mitochondria and chloroplasts have lost most of their genes through transfer to nucleus
Origins of peroxisomes unclear but may be same path

44. Post-translational sorting
Most proteins for mitochondria, chloroplasts, and all proteins for peroxisomes sorted post-translation
Must have sorting signal
Example- protein destined for mitochondrial matrix