Cell Biology: Compartments and Protein Sorting

Cell Compartments and Protein Sorting

• Cells compartmentalize to ensure materials reach the correct location at the right time, facilitated by transport systems
• Compartments restrict reactions by concentrating enzymes, substrates, and regulators
• Compartments increase membrane surface area for reactions like oxidative phosphorylation
• Membranes are generally impermeable so specialized transport mechanisms are essential for molecules to enter/interact with compartments

Intracellular Compartments

• Nucleus and cytosol (connected by pore complexes)
• Organelles in secretory/endocytic pathways (ER, Golgi, endosomes, lysosomes, peroxisomes)
• Mitochondria

Membrane Types in Cells

• Table 12-2: Shows relative amounts of membrane types in liver hepatocytes and pancreatic exocrine cells
• Plasma membrane
• Rough ER membrane
• Smooth ER membrane
• Golgi apparatus membrane
• Mitochondrial membranes (outer and inner)
• Nucleus membrane (outer/inner)
• Lysosome membrane
• Peroxisome membrane
• Endosome membrane

Compartmentalization within Cells

• Various organelles occupy different percentages of cell volume (cytosol, mitochondria, rough ER, smooth ER, Golgi, nucleus, peroxisomes, lysosomes, endosomes)
• The relationship between volume and surface area of different cell compartments is not always proportional, allowing for varied functions in different types of cells.

Electron Microscopy

• Electron microscopy images of organelles/cell structures can be misleading due to artifacts rather than actual structures.
• Electron-dense materials absorb more electrons in electron microscopy, showing up darker.
• Examples include lysosomes and other densely packed structures

Membrane-Bound Organelles and Biomolecular Condensates

• Organelles are primarily membrane-bound structures: mitochondria, nucleus, lysosomes
• Biomolecular condensates are compartments without membranes but still function as distinct cellular structures.

Vesicle Transport Principles

• Vesicle transport is highly regulated in both time and space, involving polarization of membranes.
• Orientation/polarity of membranes is crucial in vesicle transport (lumen of vesicle versus outer environment.)
• Polarization of membranes is critical for vesicle interactions during transport between organelles.

Protein Transport and Translocation

• Proteins destined for organelles have specific signal sequences (typically amino acid stretches).
• Co-translational transport: ribosomes attach to ER membrane as proteins synthesize, directly inserting nascent proteins into the ER lumen or membrane
• Post-translational transport: proteins are fully synthesized in the cytosol before being imported into the organelle such as ER or mitochondria utilizing distinct methods.

Endoplasmic Reticulum (ER)

• ER is involved in protein synthesis and processing (co-translational and post-translational)
• Contains translocon complexes essential for protein import.
• Contains chaperone proteins (e.g., calnexin) that assist in protein folding and quality control.

Signal Recognition Particle (SRP) and Protein Import

• SRP binds to signal sequence of nascent proteins, pausing translation until ribosome docks on the ER membrane.
• Receptor and ribosome facilitate protein import via the translocon (channel) into ER lumen.
• This process is dynamic and regulated to ensure efficient protein targeting.

Polyribosomes/Polysomes

• Clusters of ribosomes that simultaneously translate a single mRNA molecule.
• Efficient synthesis of multiple copies of protein.

Unfolded Protein Response (UPR)

• Cells respond to misfolded proteins in the ER by initiating UPR (three branches)
• UPR: aims to restore normal function but not necessarily exclude other mechanisms
• Misfolded proteins exit ER or are cleared via proteasomes for degradation (energy dependence).
• Proteasome: a protein complex not surrounded by membranes; it is a complex structure with specific functions for protein degradation.

Peroxisomes.

• Peroxisomes are membrane-bound organelles involved in detoxification (beta-oxidation, production of hydrogen peroxide-conversion to water), lipid metabolism and synthesis of certain lipids (e.g., plasmalogens).
• Peroxisomes form de novo through vesicle fusion (distinct from organelle division).
• Peroxin (PEX) proteins: transport essential fatty acids and enzymes.

Protein Transport: Mitochondria

• Mitochondria require substantial protein import due to their limited genome
• Use different translocator complexes (TOM, TIM, OXA) to import proteins, requiring energy.
• Protein import processes are selective due to signal sequences and translocator proteins.

Nuclear Transport

• Nuclear envelope has nuclear pores to allow selective transport of proteins/RNA/nucleotides between nucleus and cytosol.
• Gated regulated transport of materials (e.g., histones, RNA, proteins, nucleotides) through the nuclear pores
• Signal sequences/import receptors guide proteins through nuclear pores.
• Nuclear transport is energy-dependent (using small GTPase Ran).