Organelles at Work: Internal Membranes and the Path of a Protein

A factory you can't see

Right now, cells in your pancreas are making digestive enzymes and shipping them out to your small intestine. Cells in your salivary glands are doing the same for amylase. Each of those cells works like a factory with departments: one department reads the instructions, one builds, one checks and packages, one ships, one recycles the garbage, and one runs the power plant.

In this course, biology becomes chemistry inside cells. Before we look at the molecules themselves, we need a map of the places where they are made, used and broken down. That map is the set of organelles.

Internal membranes divide the cell into compartments

A bacterium is like a one-room workshop. A eukaryotic cell (a plant, animal, fungus or protist cell) is like a building with many rooms. The walls are internal membranes, made of the same phospholipid bilayer as the cell membrane (you will study that structure in the lesson The Fluid Mosaic Model).

Why have rooms?

• Different conditions in different places. A lysosome keeps its inside at about pH 5, while the cytosol around it is close to pH 7.2. Lysosome enzymes work best in acid, so if one leaks into the cytosol it works poorly and does less harm.
• More surface area. Many enzymes are built into membranes. The folded membranes of the ER and the inner membrane of the mitochondrion give a huge area for these reactions.
• Keeping incompatible reactions apart. A cell can build fats in the smooth ER while breaking fats down somewhere else, without one process undoing the other.
• Concentrating materials. Enzymes and their substrates packed into a small space meet more often, so reactions are faster.

The membranes that are linked by budding and fusing vesicles form the endomembrane system: the nuclear envelope, the ER, the Golgi bodies, lysosomes, vacuoles, vesicles and the cell membrane itself. Mitochondria and chloroplasts are not part of it; they are not linked to the other membranes by vesicles (they import their proteins directly from the cytosol), and they grow and divide on their own.

The organelles and their jobs in cellular processes

• Nucleus. Holds the DNA. Genes are copied into messenger RNA (mRNA), which leaves through nuclear pores. The nucleolus assembles ribosome parts. (You will study this in detail in Molecular Genetics.)
• Ribosomes. Read mRNA and join amino acids into proteins. Free ribosomes in the cytosol make proteins that stay in the cytosol. Bound ribosomes on the rough ER make proteins that will be secreted, put into membranes, or sent to lysosomes.
• Rough ER. As the protein is made, it is threaded into the ER's inner space (the lumen), where it folds, may form disulfide bridges, and often gets short sugar chains attached (it becomes a glycoprotein).
• Smooth ER. Makes lipids, including phospholipids for new membranes and steroid hormones (cells of the adrenal glands and testes and ovaries have a lot of smooth ER). In liver cells it helps detoxify drugs and alcohol by adding chemical groups that make them more water-soluble. In muscle cells it stores and releases calcium ions that trigger contraction.
• Golgi bodies. A stack of flattened sacs with a receiving (cis) face toward the ER and a shipping (trans) face toward the cell membrane. Proteins are modified (sugar chains trimmed or added), sorted by chemical "address tags", and packed into vesicles.
• Vesicles. Carry cargo between compartments. Secretory vesicles fuse with the cell membrane and release their contents by exocytosis.
• Lysosomes. Contain dozens of kinds of hydrolytic enzymes (proteases, lipases, nucleases, carbohydrases). They digest food particles brought in by endocytosis, destroy bacteria engulfed by white blood cells, and recycle the cell's own worn-out organelles (autophagy, "self-eating").
• Vacuoles. Plant cells have a large central vacuole that stores water, ions, sugars and pigments and pushes outward on the cell wall, keeping the plant firm (turgor). Many freshwater protists use contractile vacuoles to pump out extra water. Food vacuoles form when a cell engulfs food.
• Mitochondria. Carry out the later stages of aerobic cellular respiration and make most of a cell's ATP. The inner membrane is folded into cristae, which hold the electron transport chain. (This is the main topic of Metabolic Processes.)
• Peroxisomes (not membranes of the endomembrane system, but worth knowing): break down fatty acids and some toxins. These reactions make hydrogen peroxide, which the enzyme catalase immediately breaks into water and oxygen.

How do we know? Pulse-chase experiments

In the 1960s, George Palade and his team (Palade shared the 1974 Nobel Prize in Physiology or Medicine with Albert Claude and Christian de Duve) worked out this pathway in pancreas cells. They gave the cells a short pulse of radioactive amino acids, then a long chase of ordinary ones. Only proteins made during the pulse were radioactive. By looking at cells at different times, they could watch the labelled proteins move from place to place.

The graph below shows simulated data of the same kind. Read it the way a scientist does: which compartment holds the label first, which peaks next, and where does it end up?

When an organelle fails

In Tay-Sachs disease, a lysosomal enzyme that breaks down a fatty substance in nerve cells is missing. The substance builds up inside lysosomes and damages the nervous system. Tay-Sachs is one of a group of lysosomal storage disorders. Studying these diseases helped scientists understand what each organelle normally does.