Membrane-Bound Organelles
& Compartmentalization
Master the structure and function of eukaryotic organelles, understand how membrane compartments enable specialized biochemistry, and learn key MCAT concepts in cell biology.
MCAT Biology
What Is Compartmentalization?
Eukaryotic cells use lipid bilayer membranes to create distinct internal compartments called organelles. Each organelle maintains its own chemical environment: unique pH, ion concentrations, and enzyme sets, enabling reactions that would conflict if mixed in one space.
Prokaryotes vs Eukaryotes
Prokaryotic Cell
No membrane-bound nucleus. DNA in nucleoid region. Reactions occur in cytoplasm and on plasma membrane. Examples: bacteria, archaea.
Eukaryotic Cell
Membrane-bound nucleus and organelles. Complex internal organization. Reactions compartmentalized. Examples: animals, plants, fungi, protists.
The Endomembrane System
The endomembrane system is a network of interconnected membranes: the nuclear envelope, rough ER, Golgi apparatus, lysosomes, and transport vesicles. Proteins travel through this system via vesicular transport.
The Nucleus: Command Center
1
Double membrane (nuclear envelope): Outer membrane continuous with rough ER. Contains nuclear pores for selective transport.
2
Stores DNA: Chromatin (euchromatin = active, heterochromatin = inactive). Site of DNA replication and transcription.
3
Nucleolus: Dense region within nucleus where ribosomal RNA (rRNA) is synthesized and ribosome subunits are assembled.
4
Nuclear pore complexes: Regulate passage of mRNA, proteins, and ribosomal subunits. Require nuclear localization signals (NLS) for import.
Mitochondria: The Powerhouse
Rough vs Smooth ER
Rough ER
Studded with ribosomes. Synthesizes proteins destined for secretion, membrane insertion, or lysosomes. Site of N-linked glycosylation. Continuous with nuclear envelope.
Smooth ER
No ribosomes. Synthesizes lipids and steroids. Detoxifies drugs and poisons (liver). Stores \( \text{Ca}^{2+} \) (sarcoplasmic reticulum in muscle cells).
The Golgi Apparatus: Sorting Station
1
Cis face (receiving): Faces the ER. Receives transport vesicles with newly synthesized proteins.
2
Medial cisternae: Modify proteins by O-linked glycosylation, phosphorylation, and proteolytic clipping.
3
Trans face (shipping): Faces the plasma membrane. Sorts and packages proteins into vesicles for three destinations.
4
Three destinations: Secretory vesicles (exocytosis), lysosomes (mannose-6-phosphate tag), or plasma membrane (membrane proteins).
Lysosomes & Peroxisomes
Lysosomes
Contain acid hydrolases (optimal at \( \text{pH} \approx 5 \)). Degrade macromolecules via autophagy, phagocytosis, and receptor-mediated endocytosis. Membrane \( \text{H}^+ \)-ATPase maintains acidic pH.
Peroxisomes
Contain oxidative enzymes (catalase, oxidases). Break down very long-chain fatty acids via beta-oxidation. Detoxify \( \text{H}_2\text{O}_2 \) using catalase. NOT part of endomembrane system.
Endosymbiotic Theory
Mitochondria and chloroplasts were once free-living prokaryotes engulfed by ancestral eukaryotic cells. Evidence supporting this theory:
1
Double membranes: Inner membrane from the prokaryote, outer from the host's engulfment vesicle.
2
Own circular DNA: Similar to bacterial chromosomes, replicate independently.
3
70S ribosomes: Same size as bacterial ribosomes, not eukaryotic 80S.
4
Binary fission: Divide independently of the cell cycle, similar to bacteria.
Protein Trafficking Pathway
Endomembrane vs Non-Endomembrane
| Endomembrane System | Non-Endomembrane | |
|---|---|---|
| Members | Nucleus, ER, Golgi, lysosomes, vesicles, plasma membrane | Mitochondria, chloroplasts, peroxisomes |
| Connection | Connected by vesicular transport | Independent; own DNA (mito/chloro) |
| Membrane Origin | Derived from ER membrane | Self-replicate (fission) |
| Protein Import | Signal peptide + SRP pathway | Specific targeting signals (NLS, MTS, PTS) |
| pH | Varies: \( \text{pH} = 5 \) (lysosome) to \( \text{pH} = 7 \) (ER) | Matrix \( \text{pH} \approx 8 \) (mito), peroxisome \( \text{pH} \approx 7 \) |
How to Identify Organelle Function
1
Read the context: What process is being described? Protein synthesis? Lipid metabolism? Energy production? Degradation?
2
Identify the membrane: Is the organelle single-membrane (ER, Golgi, lysosome), double-membrane (nucleus, mitochondria, chloroplast), or non-membrane (ribosome)?
3
Check the pH clue: Acidic environment = lysosome. Alkaline matrix = mitochondria. Neutral = cytosol or ER.
4
Look for targeting signals: Signal peptide = ER. Mannose-6-phosphate = lysosome. NLS = nucleus. MTS = mitochondria.
5
Eliminate by exclusion: If the answer involves detoxification of \( \text{H}_2\text{O}_2 \), it must be peroxisomes (catalase). If it involves ribosome assembly, it must be the nucleolus.
Example: Insulin Secretion Pathway
Trace the path of insulin (a secreted protein hormone) from gene to extracellular space:
1
Nucleus: Insulin gene is transcribed into mRNA. mRNA is processed (5' cap, 3' poly-A tail, splicing) and exported through nuclear pores.
2
Rough ER: Ribosomes translate mRNA. Signal peptide directs the ribosome-mRNA complex to the ER. Preproinsulin enters ER lumen, signal peptide is cleaved, forming proinsulin. N-linked glycosylation and disulfide bond formation occur.
3
Golgi apparatus: Proinsulin is further modified. C-peptide is cleaved, producing mature insulin (A and B chains). Packaged into secretory vesicles at the trans face.
4
Exocytosis: Secretory vesicles fuse with the plasma membrane upon glucose stimulation, releasing insulin into the bloodstream.
Example: Lysosomal Storage Disease
A patient has I-cell disease. Lysosomal enzymes are found secreted extracellularly instead of being delivered to lysosomes. What went wrong?
Common Mistakes
✕ Peroxisomes are endomembrane
Peroxisomes are NOT part of the endomembrane system. They self-replicate by fission, unlike lysosomes which bud from the Golgi.
✕ Free ribosomes make different proteins
Free and bound ribosomes are identical. The mRNA's signal peptide determines destination: signal peptide present = ER-bound. Not the ribosome itself.
✕ Golgi only does glycosylation
The Golgi also does proteolytic processing, phosphorylation, sulfation, and critical sorting/packaging. It is a modification AND sorting center.
Question 1 of 5
A researcher discovers that a protein lacks a signal peptide. Where will this protein most likely be found after translation?
Without a signal peptide, the ribosome-mRNA complex is not directed to the ER by SRP. Translation completes on free ribosomes in the cytosol, and the protein remains in the cytosol (or is targeted to other organelles via different signals like NLS or MTS).
Question 2 of 5
Which of the following provides the strongest evidence for the endosymbiotic theory of mitochondrial origin?
Mitochondria have circular DNA (like bacteria), 70S ribosomes (bacterial-type, not eukaryotic 80S), and a double membrane (not single). They are found in eukaryotes, not prokaryotes. These bacterial-like features strongly support endosymbiotic origin.
Question 3 of 5
A drug inhibits the \( \text{H}^+ \)-ATPase on the lysosomal membrane. What is the most direct consequence?
The \( \text{H}^+ \)-ATPase actively pumps protons into the lysosome to maintain its acidic pH (\( \text{pH} \approx 5 \)). Inhibiting this pump causes the pH to rise toward neutral, which denatures acid hydrolases and prevents degradation of substrates. Protein entry and Golgi vesicle formation are not directly affected.
Question 4 of 5
A cell biologist treats cells with brefeldin A, which disrupts vesicle transport from the ER to the Golgi. Which process would be most directly impaired?
Brefeldin A blocks ER-to-Golgi vesicle transport. Secretory proteins must travel through the ER and Golgi to reach the plasma membrane. Blocking this pathway directly impairs protein secretion. DNA replication, oxidative phosphorylation, and rRNA transcription occur in organelles not on this pathway.
Question 5 of 5
Which organelle is correctly paired with its function?
Peroxisomes contain catalase, which breaks down \( \text{H}_2\text{O}_2 \) into water and oxygen. Smooth ER handles lipid synthesis and detoxification (not ribosome assembly: that is the nucleolus). Rough ER handles protein synthesis (not lipid synthesis). Oxidative phosphorylation occurs in mitochondria (not the Golgi).