Organelles of Eukaryotic Cells AHMP 5406

Objectives List the principle functions and describe the structure of the nucleus, mitochondrion, endoplasmic reticulum, Golgi, lysosomes and peroxisomes in higher eukaryotes Describe the modification and transport of proteins from the ER through the Golgi Describe the intracellular transport of proteins from the trans Golgi network to lysosomes Describe the structure of the mitochondrion and the process of ATP synthesis Describe the contribution of organellar dysfunction to the development of disease

Basic eukaryotic organelles Nucleus Endoplasmic reticulum (ER) Golgi Peroxisomes Lysosomes Mitochondria

General eukaryotic cell

How molecules are transported around the cell…

The Nucleus

Nucleus The largest organelle in eukaryotes Surrounded by 2 phospholipid bilayers Inner nuclear membrane defines the nucleus itself Outer nuclear membrane is continuous with the rough ER Space between the inner and outer membranes is continuous with the lumen of the rough ER

Nucleus The two nuclear membranes fuse at the nuclear pores which regulate movement of molecules between nucleus and cytosol Contains the DNA of eukaryotic cells DNA is packaged into chromosomes in metabolically active nuclei (growing or differentiating cells) The cell’s rRNA is synthesized in the nucleolus (a suborganelle)

Nucleus

How molecules are transported around the cell…

The nucleus

The nucleus

The nucleus

Ran GTPases drive directional transport through nuclear pore complexes Ran is a molecular switch Two conformations dependent on what is bound to it Ran-GEF is in the nucleus GDP to GTP “Cocks the hammer” Creates a gradient Ran-GAP is in the cytosol GTP to GDP Uses energy to import “pulls the trigger”

The Endoplasmic Reticulum

Endoplasmic reticulum Second largest cellular organelle Has many functions, but primarily important in the synthesis of membrane lipids and proteins Two types: rough and smooth

Smooth Endoplasmic reticulum Functions in synthesis of fatty acids and phospholipids Abundant in hepatocytes enzymes in SER detoxify hydrophobic chemicals such as pesticides and carcinogens to water soluble compounds that can be excreted High doses of these compounds result in LOTS of SER proliferation

Rough Endoplasmic reticulum Ribosomes bound to the surface make it “rough” Responsible for synthesis membrane and organellar proteins and virtually all proteins that are to be secreted from the cell Ribosomes that make these proteins are bound to the ER by the newly growing peptide chain The newly made protein passes through the RER with the help of specific proteins These new proteins accumulate in the lumen of the RER and await transport Very abundant in cells that produce secreted proteins: plasma cells (antibodies), pancreatic acinar cells (digestive enzymes)

Endoplasmic reticulum

Endoplasmic reticulum

Endoplasmic reticulum

How the endoplasmic reticulum probably came to be…

The Golgi Complex

Golgi Responsible for protein modification and transport Divided into the cis-, medial and trans- Golgi Transfer vesicles from the ER fuse with the cis- region and deposit proteins After movement through the Golgi, they bud off through the trans- side

Golgi

Golgi

Transport of proteins from trans-Golgi to lysosomes Lysosomal hydrolases carry a maker Mannose 6-phosphate (M6P) M6P groups are recognized by M6P receptor proteins in trans-Golgi Bind to lumenal side by way of adaptins Adaptins interact with clathrin molecules on the cytosolic side Shuttled to late endosome where pH change releases hydrolase

Peroxisomes

Peroxisomes Contain oxidases – enzymes that generate hydrogen peroxide Large amounts of catalase – degrades hydrogen peroxide to water and oxygen Oxidation is NOT linked to ATP generation Produce acetyl groups that are used in the production of cholesterol and biosynthetic molecules in animal cells Also degrade toxins produced by liver, kidney cells, etc.

Peroxisomes

Peroxisome-assembly related diseases X-linked adrenoleukodystrophy (ADL) Defective oxidation of very long chain fatty acids ADL gene encodes the peroxisomal membrane protein that transports an oxidative enzyme into the peroxisomes Effects are evident in mid-childhood: severe neurological disorders followed by death within a few years

Peroxisome-assembly and function related diseases Pseudo-Zellweger syndrome Beta-oxidation disorder (fatty acid metabolism) Other peroxisomal functions remain intact Symptoms are present at birth Major body systems are affected: vision, kidneys, cartilage, heart, muscle and liver

Lysosomes

Lysosomes Acidic organelles – pH4.8 Contain degradative enzymes (acid hydrolases): nucleases, proteases, phosphatases, etc. Can degrade intracellular components, phagocytized or endocytized items May be several hundred in a typical animal cell Degrade themselves by autophagy

Lysosomes

Lysosomes

Lysosomal Storage Diseases Caused by genetic defects Result in accumulation of undigested substrates in lysosomes Usually act on nervous system Hurler’s syndrome Caused by mutation on gene that codes for enzyme that breaks down glycosaminoglycan Results in deformation and retardation I-cell disease Severe form of Hurler’s syndrome Detected by inclusion bodies in tissue cells Cell hydrolases are misdirected and secreted

Tay Sachs Disease 1 in 27 Jews in the U.S. are carriers of the defective Hex-A gene Frequency in the general population is 1 in 250 Over 50 DNA mutations have been identified in the Hex-A gene DNA testing is usually done in conjunction with biochemical testing for Hex-A levels in the blood

Tay Sachs Disease Individuals are lacking the ability to break down gangliosides (glycolipids) Symptoms usually appear before age 1 Children become blind and demented by age 2 Usually fatal by age 3 Nerve cells are greatly enlarged with swollen, lipid-filled lysosomes

How molecules are transported around the cell…

Mitochondria

Mitochondria Up to 25% of cytoplasm volume Main site of ATP production Inner and outer membrane Outer membrane allows molecules up to 10,000 mw to pass through, much like gram negative bacteria Inner membrane is composed of cristae that function to increase oxidative surface area

Mitochondria Fuels for ATP synthesis are fatty acids and glucose Degradation of 1 glucose to CO2 and H2O can yield up to 36 ATP molecules Initial stage producing 2 ATPs’ occurs in the cytosol Terminal stages producing up to 34 ATP’s are carried out by mitochondrial enzymes in the matrix and cristae

Mitochondria

How the mitochondrion probably came to be…

Summary Points All eukaryotic cells contain a membrane bound nucleus and organelles in their cytosol Lysosomes, which are found only in animal cells, have an acidic interior and contain various hydrolases used to break down cellular components Peroxisomes are small organelles containing enzymes that oxidize various organic compounds, generating hydrogen peroxide

Summary Points Mitochondria are bound by two membranes, the inner one extensively folded. Enzymes in the inner mitochondrial membrane and central matrix carry out the terminal stages of sugar and lipid oxidation coupled to ATP synthesis Secretory and membrane proteins are synthesized on the RER (a network of membrane vesicles studded with ribosomes). These proteins move to the Golgi complex where they are stored and processed

Summary Points The nucleus is surrounded by an inner and an outer membrane. Movement of molecules into and out of the nucleus occurs through the nuclear pores. The outer nuclear membrane is continuous with the RER. The cytosol is the portion of the cell’s interior that remains after you take away all of the organelles. There are a lot of proteins in it – lots of soluble enzymes, actin microfilaments, microtubules and intermediate filaments. These help to give the cell some sort of structure.

General eukaryotic cell