lecture 2 - Organelles in Neuronal cells Flashcards
1
Q
What is a cell
A
A cell is defined as the smallest, basic unit of life that is responsible for all of life’s processes
2
Q
Cells fall into one of two broad categories
A
prokaryotic and eukaryotic.
The predominantly single-celled organisms of the domains Bacteria and Archaea are classified as prokaryotes (pro– = before; –karyon– = nucleus).
Animal cells, plant cells, fungi, and protists are eukaryotes (eu– = true; –karyon– = nucleus).
3
Q
A prokaryotic cell
A
is a simple, single-celled (unicellular) organism that lacks a nucleus, or any other membrane-bound organelle.
4
Q
A eukaryotic cell
A
is a cell that has a membrane-bound nucleus and other membrane-bound compartments or sacs, called organelles, which have specialized functions.
5
Q
All cells share four common components
A
1) a plasma membrane, an outer covering that separates the cell’s interior from its surrounding environment.
2) cytoplasm, consisting of a jelly-like region within the cell in which other cellular components are found.
3) DNA, the genetic material of the cell; and
4) ribosomes, particles that synthesize proteins.
However, prokaryotes differ from eukaryotic cells in several ways, which can be seen on the table.
6
Q
What are organelles?
A
An organelle is a subcellular structure that has one or more specific jobs to perform in the cell, much like an organ does in the body. Among the more important cell organelles are the nuclei, which store genetic information; mitochondria, which produce chemical energy; and ribosomes, which assemble proteins.
7
Q
Organelles without a membrane
A
The cell wall, ribosomes and cytoskeleton are non-membrane bound organelles
The are present in both prokaryotic and eukaryotic cells
Prokaryotic are unicellular, lack nucleus and membrane-bound organelles.
8
Q
Single membrane-bound organelles
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Vacuole, lysosome, Golgi apparatus, endoplasmic reticulum are single membrane-bound organelles
9
Q
Double membrane-bound organelles
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Nucleus and mitochondria are double membrane-bound organelles
10
Q
Cells as a ‘factory’
A
Examples:
The plasma membrane – ‘guarded gate’, where credentials are checked before entry.
The nucleus – headquarters or CEO Office, where CEO with managers will decide on products and give timely instruction for production.
The cytoplasm – factory floor, where everything products are assembled, finished and shipped.
11
Q
Cytoplasm – ‘Factory Floor’
A
In eukaryotic cells, the cytoplasm includes all of the material inside the cell and outside of the nucleus.
The portion of the cytoplasm that is not contained in the organelles is called the cytosol.
A framework of protein scaffolds called the cytoskeleton provides the cytoplasm and the cell with their structure. Along with the centrosome (a cellular structure involved in the process of cell division).
12
Q
Cell/Plasma Membrane – ‘Guarded Gate’
A
- The membrane consists of a fluid phospholipid bilayer with proteins embedded in it.
- Integral membrane proteins interact with the hydrophobic ‘tails’ of lipid molecules within the lipid bilayer; some of these proteins are transmembrane proteins that act as channels (pores) for transport of molecules into and out of the cell.
- Peripheral proteins interact only with the outer hydrophilic ‘heads’ of the lipid molecules.
- Membrane lipids and proteins are often glycosylated, i.e. attached to sugar chains.
13
Q
Cell/Plasma Membrane – ‘Guarded Gate’
A
14
Q
Cell/Plasma Membrane – ‘Guarded Gate - Selective transport
A
Specialized proteins in the cell membrane regulate the concentration of specific molecules inside the cell.
15
Q
Examples of the action of transmembrane proteins
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- Transporters carry a molecule (such as glucose) from one side of the plasma membrane to the other.
- Receptors can bind an extracellular molecule (triangle), and this activates an intracellular process.
- Enzymes in the membrane can do the same thing they do in the cytoplasm of a cell: transform a molecule into another form.
- Anchor proteins can physically link intracellular structures with extracellular structures.
16
Q
Fluid mosaic model
A
The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components —including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
17
Q
What are the key functions and properties of the cell membrane?
A
Regulates entry and exit of substances.
Facilitates communication and information sharing between cells.
Flexible, allowing growth, shape change, and movement.
Self-healing, able to reseal if pierced.
18
Q
What is meant by the semi-permeability of the cell membrane?
A
Allows rapid diffusion of small hydrophobic molecules (e.g., oxygen, carbon dioxide).
Small polar molecules (e.g., water, ethanol) pass through slowly.
Restricts highly charged molecules (e.g., ions) and large molecules (e.g., sugars, amino acids).
Transport proteins enable passage of restricted molecules.
19
Q
The Lipid Bilayer
A
20
Q
A phospholipid
A
is an amphipathic molecule, meaning it has both a hydrophilic region and a hydrophobic region
Phospholipids have two fatty acid tails attached to glycerol, unlike fat molecules with three.
The third hydroxyl group of glycerol is attached to a negatively charged phosphate group.
Often, a small charged or polar molecule (e.g., choline) is linked to the phosphate group.
21
Q
How does the phospholipid bilayer form, and what is its arrangement in the cell membrane?
A
Forms two adjacent layers, creating a bilayer.
Fatty acid tails (hydrophobic) face inward, away from water.
Phosphate heads (polar and hydrophilic) face outward toward the aqueous environment, one layer exposed to the cell interior and one to the exterior.
22
Q
How do the properties of phospholipids affect membrane fluidity?
A
Unsaturated fatty acids with double bonds create kinks, preventing tight packing and lowering melting point.
Shorter fatty acid chains reduce van der Waals forces, also lowering melting point.
These properties regulate membrane fluidity at different temperatures.
23
Q
What roles do membrane transport proteins play in the cell?
A
Transport molecules selectively and specifically.
Use energy to move nutrients against concentration gradients.
Maintain concentration gradients crucial for cell health.
Enable accumulation of nutrients and disposal of waste
24
Q
What is the function of receptor proteins in the cell membrane?
A
Bind specific signals, such as hormones or immune mediators.
Trigger conformational changes that transmit signals to intracellular messengers.
Facilitate communication within and between cells
25
The fluid mosaic model
describes the structure of the plasma membrane as a mosaic of components —including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character
26
What are steroids, and why is cholesterol important in animals?
Steroids are lipids with a carbon skeleton of four fused rings.
Cholesterol is essential for cell membranes and a precursor for other steroids like sex hormones.
It acts as a neurosteroid, influencing brain activity by modulating neurotransmitter receptors
27
What roles does cholesterol play in cell membranes?
Makes up 25-30% of cell membrane lipids.
Enhances fluidity by preventing tight packing of phospholipids at low temperatures.
Reduces permeability by filling spaces between phospholipids.
Hydrophilic hydroxyl group interacts with water; hydrophobic domain integrates with lipid tails, maintaining integrity.
28
What distinguishes prokaryotic cells from eukaryotic cells regarding the nucleus?
Prokaryotic cells lack an organized nucleus.
Eukaryotic cells have membrane-bound nuclei that house DNA and direct ribosome and protein synthesis.
29
What are the main structural features of the nucleus in eukaryotic cells?
Largest organelle in animal cells, averaging 6 μm in diameter, occupying ~10% of cell volume.
Contains chromatin stored in nucleoplasm.
Surrounded by a double membrane (nuclear envelope) with a space of 20–40 nm between layers.
Outer membrane is continuous with the rough endoplasmic reticulum
30
How do nuclear pores and nuclear lamins contribute to the nucleus’s function?
Nuclear Pores: Rosette-shaped protein complexes (~100 nm in diameter) regulate material movement into and out of the nucleus (e.g., RNA out, proteins in).
Nuclear Lamins: Meshwork of intermediate filaments that support the nuclear membrane.
31
What is the nucleolus, and what occurs there?
A dense structure in the non-dividing nucleus.
Synthesizes ribosomal RNA (rRNA) based on DNA instructions.
rRNA combines with ribosomal subunits, which exit the nucleus via nuclear pores.
32
How are ribosomes and protein synthesis linked to the nucleolus?
Ribosomal subunits from the nucleolus are assembled into ribosomes in the cytoplasm.
Ribosomes synthesize proteins either:
On free ribosomes (cytoplasmic use).
On rough ER-bound ribosomes (transported to the ER, Golgi apparatus, and packaged for secretion).
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Ribosomes – ‘Machines’
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Nucleolus - types of chromatin
The darker region next to the nuclear envelope is heterochromatin, which is a tightly packed form of DNA. The genes located in the tightly packed form of DNA are less active in their transcription (ie. less expressed).
In contrast, the genes located in the euchromatin, which are lighter regions in the electron microscopic image, are more active in transcription.
33
What are ribosomes, and where are they found?
Ribosomes are ribonucleoproteins made of RNA and proteins, responsible for building proteins.
Composed of a large and small subunit.
Found either free in the cytoplasm or bound to the rough ER.
Appear as clusters (polyribosomes) or single dots under an electron microscope.
34
what are the roles of ribosomal subunits and sites during protein synthesis?
Small subunit: Binds to mRNA and the large subunit.
Large subunit:
P site: Holds tRNA with the growing polypeptide chain.
A site: Holds tRNA with the next amino acid to be added.
E site: Releases discharged tRNA (exit site).
35
What does the Svedberg (S) value of ribosomes indicate?
Reflects the sedimentation rate during centrifugation, based on size and shape.
Eukaryotic ribosomes: 80S (40S + 60S).
Prokaryotic ribosomes: 70S (30S + 50S).
S values do not add up due to differences in shape and size affecting sedimentation.
36
What are the two main processes of protein synthesis?
Transcription:
Takes place in the nucleus.
DNA is used as a template to synthesize mRNA.
mRNA carries genetic instructions from DNA to the ribosome.
Translation:
Occurs in the cytoplasm at a ribosome.
Ribosome reads mRNA codons, and tRNA brings amino acids in the correct sequence.
Polypeptide chain is assembled based on the mRNA code.
37
What is the central dogma of molecular biology?
Describes the flow of genetic information: DNA → RNA → Protein.
Transcription: DNA → RNA (mRNA synthesis in the nucleus).
Translation: RNA → Protein (polypeptide synthesis at the ribosome).
38
What are the stages of translation in protein synthesis?
Initiation: Ribosome assembles around the mRNA and the start codon is recognized.
Elongation: tRNA brings amino acids to the ribosome, and the polypeptide chain grows.
Termination: The ribosome reaches a stop codon, and the completed polypeptide is released.
39
What is the endomembrane system, and which organelles are part of it?
A system in eukaryotic cells that modifies, packages, and transports lipids and proteins.
Includes: nuclear envelope, lysosomes, vesicles, endoplasmic reticulum, Golgi apparatus, and plasma membrane.
40
Are ribosomes and the plasma membrane part of the endomembrane system?
Plasma membrane: Part of the system as it interacts with endomembrane organelles.
Ribosomes: Not part of the system since they are not made of membrane, despite being on the rough ER.
41
What are the main functions of the endoplasmic reticulum (ER) in the cell?
Synthesizes membrane lipids and proteins.
Produces transmembrane proteins and lipids for most organelles.
Modifies and transports proteins like a factory’s "conveyor belt."
42
What is the structure of the endoplasmic reticulum (ER)?
Consists of membranous tubules and sacs called cisternae.
Divides the ER lumen (internal compartment) from the cytosol.
Rough ER: Studded with ribosomes for protein synthesis.
Smooth ER: Lacks ribosomes, appearing smooth.
43
What are the main functions of the smooth endoplasmic reticulum (ER)?
Lipid synthesis
The SER makes lipids, including phospholipids for plasma membranes.
Steroid hormone production
The SER produces steroid hormones, such as those found in the adrenal cortex and endocrine glands.
Carbohydrate metabolism
The SER breaks down and builds up carbohydrates, such as sugars and starches.
Calcium ion storage
The SER stores calcium ions in muscle cells, which helps with muscle contraction.
Detoxification
The SER breaks down harmful substances and turns them into safer substances.
Glucose mobilization
The SER mobilizes glucose from glycogen, especially in liver, kidney, and intestinal cells
44
Why is smooth ER abundant in certain cells?
Cells involved in hormone production (e.g., testes, ovaries) have abundant smooth ER for steroid synthesis.
Liver cells rely on smooth ER for detoxifying drugs and poisons.
45
What are the main functions of the rough endoplasmic reticulum (ER)?
Protein synthesis by ribosomes on its surface.
Protein folding and post-translational modifications (e.g., glycosylation, disulfide bond formation).
Quality control of proteins, including assistance from chaperone proteins.
Transport of proteins to other cell areas or the Golgi apparatus for further processing.
46
how are proteins processed in the rough ER?
Ribosomes synthesize proteins based on mRNA instructions.
Nascent polypeptide chains enter the ER lumen for folding and modifications.
Misfolded or aberrant proteins are identified and managed by quality control mechanisms.
Chemically modified proteins are transported for use or further processing.
47
How is protein synthesis directed to free ribosomes or the rough ER (RER)?
Translation begins on free ribosomes for all mRNAs.
Proteins destined for lysosomes, secretion, or membranes undergo cotranslational localisation.
A signal sequence near the N-terminus is recognized by the signal recognition particle (SRP), pausing translation.
The ribosome-mRNA-polypeptide complex is directed to the RER, where translation resumes and the polypeptide is translocated into the ER lumen.
48
What are the steps of cotranslational targeting of secretory proteins to the ER?
Signal sequence on the polypeptide is recognized and bound by the SRP.
SRP escorts the complex to the ER membrane, binding to the SRP receptor.
SRP is released, and the ribosome binds to a Sec61 translocation complex, inserting the signal sequence into a membrane channel.
Translation resumes, and the growing polypeptide chain is translocated across the membrane.
Signal peptidase cleaves the signal sequence, releasing the polypeptide into the ER lumen.
49
What are the main functions of the Golgi apparatus?
Acts as the sorting and packing center for proteins and lipids.
Sorting: Receives proteins and lipids from the ER and sorts them based on molecular 'labels.'
Glycosylation: Completes glycosylation (attachment of sugar molecules) and other modifications to ensure proteins are properly structured and functional.
Packaging: Packages sorted proteins and lipids into vesicles for one of three destinations:
Lysosomes: For intracellular digestion.
Plasma membrane: For integration into the cell membrane.
Secretion: For export out of the cell via exocytosis.
50
How is the Golgi apparatus structured and organized?
Location: Found near the nucleus.
Structure: Composed of stacks of membrane-bound sacs called cisternae (typically 3–6 in a stack).
Two faces:
Cis face (entry): Faces the ER; receives vesicles containing proteins and lipids.
Trans face (exit): Faces away from the ER; vesicles bud off to transport materials to their final destinations.
51
What are the three main sections of the Golgi apparatus and their roles?
Cis Golgi network (Goods inwards):
Entry point for materials from the rough ER.
Follows transitional elements of the ER (also called ER-Golgi intermediate compartments, or ERGIC).
Golgi stack (Main processing area):
Consists of three layers: cis cisternae, medial cisternae, and trans cisternae.
Proteins and lipids are modified as they move through these layers.
Trans Golgi network (Goods outwards):
Final sorting and concentration of materials.
Vesicles bud off the trans face for transport to lysosomes, plasma membrane, or secretion.
52
How does the Golgi apparatus work with the ER in protein and lipid transport?
The rough ER sends proteins and lipids to the cis Golgi network in vesicles.
The Golgi modifies and labels them in the Golgi stack (cis, medial, and trans cisternae).
Final products are sorted and packaged in the trans Golgi network, forming vesicles for specific destinations (lysosomes, plasma membrane, or secretion).
53
Why is the Golgi apparatus crucial for cell function?
Ensures proteins and lipids are properly modified and functional.
Sorts and directs cellular materials to the correct location.
Packages materials for transport within the cell or secretion outside the cell, maintaining efficient cellular operations.
54
How are proteins modified in the Golgi apparatus?
Proteins from the ER are taken up by the cis Golgi and modified as they pass through the stack.
Modifications build on initial ER alterations, such as the addition or trimming of sugars and lipids.
Glycoproteins undergo specific changes:
Lysosomal proteins are phosphorylated on mannose sugars, forming mannose-6-phosphate for lysosomal targeting.
Plasma membrane and secreted proteins have three mannose sugars removed.
55
What ensures proteins reach their correct destination after processing in the Golgi?
Proteins destined for lysosomes are tagged with mannose-6-phosphate in the cis Golgi, recognized by receptors in the trans Golgi.
Plasma membrane and secreted proteins are modified differently to suit their specific destinations.
From the trans Golgi, proteins are packaged into vesicles for delivery to their final destinations.
56
Vesicles – ‘Factory trolleys’
57
How do vesicles transport proteins from the Golgi to their destinations?
Proteins are packaged into vesicles at the trans face of the Golgi.
Vesicles transport proteins to:
The plasma membrane for incorporation or secretion.
Lysosomes, using the mannose phosphate tag for targeting.
Vesicles shed their coat before fusing with their target membrane.
58
What are the different types of coated vesicles and their functions?
Clathrin-coated vesicles: Involved in endocytosis and secretion.
COPI-coated vesicles: Transport proteins between Golgi cisternae.
COPII-coated vesicles: Carry proteins from the ER to the cis Golgi.
Coat proteins assist in vesicle identification and cargo selection.
59
Vesicle formati
The coat protein forms the curved bud membrane configuration. This comes about as a result of the interaction of the coat protein molecules with each other to form a curved cage.
The cargo molecules are picked up by the cargo receptor, which is a transmembrane protein. The cargo binding site is on the lumen side of the protein.
The cargo receptor/cargo complex is recognized by adaptin which combines with the cytosolic side of the adaptin molecule.
The cargo/ cargo receptor/ adaptin complex then combines with the coat protein on the cytosolic surface. This is very important for selection and concentration of cargo proteins. Each coat protein unit has binding sites for several adaptin molecules, and thus cargo receptors and their cargo. This results in concentration of cargo molecules in the area where the bud is forming.
Dynamin constricts the neck of the bud (vesicle), which then pinches off. This is an ATP driven process.
Uncoating then occurs as the coat protein and adaptin are released and recycled.
60
These processes are common to all vesicle type formation.
This process requires the interaction of several components: cargo receptor, adaptin, coat protein (COP or clathrin)
and dynamin. The essential point is that the coat protein brings about both formation of the bud and concentration of
cargo protein.
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Vesicle Formation, Targeting and Fusion
SNAREs facilitate selective targeting and fusion by forming coiled coils between v-SNAREs on the vesicle membrane and t-SNAREs on the target membrane.
While crucial, SNAREs are complemented by other proteins. Rab proteins aid in vesicle tethering, SNAPs stabilise pre-fusion complexes, and NSFs dissociate SNARE complexes post-fusion.
In nerve cells, SNAREs play a critical role in synaptic vesicle docking and fusion at terminals.
62
Overview of the endomembrane system.
63
What are the main functions of lysosomes?
Breakdown and digestion of macromolecules (carbohydrates, lipids, proteins, and nucleic acids).
Repair of the cell membrane.
Defense against foreign substances like bacteria, viruses, and antigens.
64
How do lysosomes help the cell obtain energy?
Release enzymes to break down complex molecules (e.g., sugars, proteins) from food into usable energy.
When food is unavailable, lysosomal enzymes digest the cell's own organelles to obtain necessary nutrients.
65
What enzymes do lysosomes contain, and what is their optimal environment?
Contain ~50 degradative enzymes (acid hydrolases) that break down proteins, DNA, RNA, polysaccharides, and lipids.
Enzymes are active at acidic pH (~5), maintained by a proton pump using ATP to concentrate H+ ions.
Enzymes are inactive at neutral pH (~7.2), preventing uncontrolled digestion.
66
How do lysosomes contribute to immune defense?
In macrophages, pathogens are engulfed via phagocytosis, forming vesicles.
These vesicles fuse with lysosomes, where degradative enzymes break down the pathogens.
67
What enzymes are present in lysosomes, and what are their functions?
Nucleases: Break down RNA/DNA into mononucleotides.
Proteases: Degrade proteins and peptides.
Phosphatases: Remove phosphate groups.
Enzymes also target complex polysaccharides and lipids, breaking them into monomeric subunits.
68
What causes Tay-Sachs disease, and how does it affect lysosomal function?
Caused by a deficiency of hexosaminidase A, leading to accumulation of gangliosides in brain and nerve cells.
Disrupts lysosomal function, preventing the breakdown of glycosphingolipids.
Results in enlarged nerve cells with lipid-filled lysosomes, nerve cell degeneration, and an inflammatory response.
Symptoms include mental impairment, blindness, and early death, typically before age 3.
69
What are peroxisomes, and where are they found?
Peroxisomes are small organelles (0.2–1 μm in diameter) surrounded by a single membrane.
Found in all animal cells (except erythrocytes) and many plant cells.
Lack nucleic acids and are not derived from a bacterial ancestor.
Peroxisomal proteins are encoded by nuclear genes and incorporated after translation in the cytoplasm.
70
What are the main functions of peroxisomes?
Contain oxidases, enzymes that oxidize organic substances using molecular oxygen, producing hydrogen peroxide (H₂O₂).
Perform oxidative reactions, including the breakdown of fatty acid molecules.
Manage hydrogen peroxide safely, preventing cellular damage.
71
What are the main enzymatic functions of peroxisomes?
Oxidases: Remove hydrogen atoms from organic substrates, producing hydrogen peroxide (H₂O₂) (e.g., RH₂ + O₂ → R + H₂O₂).
Catalase:
Uses H₂O₂ to oxidize other substrates (e.g., phenols, alcohols) via the reaction H₂O₂ + R′H₂ → R′ + 2H₂O.
Breaks down excess H₂O₂ into water and oxygen (H₂O₂ → O₂ + 2H₂O), preventing cellular damage.
Important for detoxification in liver and kidney cells, including ethanol oxidation to acetaldehyde.
72
what biosynthetic and clinical roles are associated with peroxisomes?
Biosynthesis: Catalyze the first reactions in the formation of plasmalogens, which make up ~70% of myelin sheath.
Clinical impact:
Deficiency in plasmalogens leads to hypomyelination, causing neurological abnormalities.
Zellweger syndrome:
Caused by mutations in peroxins, impairing peroxisome assembly.
Leads to accumulation of long-chain fatty acids and brain dysfunction (e.g., hypomyelination, neuronal migration defects).
Symptoms: Craniofacial abnormalities, hepatomegaly, renal cysts, profound hypotonia, seizures, and feeding difficulties.
73
What are the key characteristics of mitochondria?
Known as the "powerhouses" of the cell, producing ATP through cellular respiration.
Surrounded by a double membrane system:
Outer membrane: Smooth and protective.
Inner membrane: Folded into cristae to increase surface area for energy production.
Contain their own genome and replicate independently of the cell.
Resemble bacteria in size (0.5–10 μm) and shape, a relic of their prokaryotic ancestry.
74
How does the number and structure of mitochondria vary in different cell types?
The number of mitochondria depends on the cell’s energy demands:
Sperm tails: Mitochondria run in a spiral along the length of the tail.
Heart muscle cells: Mitochondria occupy ~40% of cytoplasmic space.
Liver cells: 20–25% of cytoplasmic space with ~1000–2000 mitochondria per cell.
Cristae in the inner membrane increase the surface area for energy production.
75
What is the difference in permeability between the inner and outer mitochondrial membranes?
Outer membrane: Freely permeable to small molecules and ions due to protein channels called porins, allowing diffusion of molecules up to ~6000 Daltons.
Inner membrane: Highly selective, restricting permeability; loaded with proteins involved in electron transport and ATP synthesis.
76
What does the mitochondrial matrix contain, and what are its functions?
Contains the mitochondrial genetic system (DNA, RNA, and ribosomes).
Houses enzymes responsible for central reactions of oxidative metabolism, critical for energy production.
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78
How is the mitochondrial genome distinct from the nuclear genome?
Mitochondrial DNA is circular, similar to bacterial genomes, and exists in multiple copies per organelle.
Mitochondrial genome: 16,569 base pairs.
Nuclear genome: 3.3 billion base pairs.
Mitochondria contain their own genetic system, separate from the nucleus.
79
what does the mitochondrial genome encode, and why does it rely on the nuclear genome?
Encodes 37 genes:
13 proteins for the oxidative phosphorylation system.
22 tRNAs and 2 rRNAs.
Mitochondria depend on nuclear gene products for many of their proteins, as the small mitochondrial genome cannot support full functionality independently.
80
Import of proteins into mitochondria
Proteins are targeted for mitochondria by an amino-terminal presequence containing positively charged amino acids.
Proteins are maintained in a partially unfolded state by association with a cytosolic Hsp70 and are recognised by a receptor on the surface of mitochondria.
The unfolded polypeptide chains are then translocated through the Tom complex in the outer membrane and transferred to the Tim complex in the inner membrane.
The voltage component of the electrochemical gradient is required for translocation across the inner membrane.
The presequence is cleaved by a matrix protease, and a mitochondrial Hsp70 binds the polypeptide chain as it crosses the inner membrane, driving further protein translocation.
A mitochondrial Hsp60 then facilitates folding of the imported polypeptide within the matrix.
81
What are mitochondrial diseases, and how do they manifest?
Mitochondrial diseases can affect multiple or single organs, including the brain, liver, heart, or optic nerve.
Disorders may change over time, as in Pearson syndrome:
Initially causes pancreatic dysfunction and anemia.
Survivors may later develop brain disease.
Typically progressive and can manifest in children or adults.
82
what causes mitochondrial damage, and how is it categorized?
Primary damage:
Caused by genetic defects in mitochondrial DNA or nuclear genes essential for mitochondrial function.
Often affects energy-intensive organs (e.g., brain, heart) and manifests in children or adults (e.g., blindness, diabetes).
Secondary dysfunction:
Results from life events like heart attacks or conditions like sepsis, neurodegenerative diseases, cancer, autoimmune diseases, and ageing.
Linked to disorders like Alzheimer’s, Parkinson’s, diabetes, and obesity.
