BIOB10H3 Lecture Notes - Lecture 7: Maple Syrup Urine Disease, Force H, Intermembrane Space
25 Jun 2018
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Lecture 7: Mitochondria
Mitochondria
arose from phagocytosis of aerobic prokaryote
can divide in the cell: “mitochondrial fission”
“powerhouse of the cell”
Functions:
osite of aerobic respiration
outilizing oxygen to extract energy from macromolecules (primarily glucose) and converting it to
ATP
ATP Production
we use 2x1026 molecules of ATP/day
ATP – cells’ energy source energy is released when ATP is hydrolyzed to ADP + Pi
Many mitochondria in: muscle cells, liver cells, fat cells, plant cells & sperm cells
Parts of the Mitochondria
1. Outer Mitochondrial Membrane (OMM)
50% protein:lipid ratio
Contain porin proteins - large channels
obacterial protein
Allow very large molecules through
2. Inner Mitochondrial Membrane (IMM)
Cristae - many thin folds of IMM to increase the surface area
IMM is 75% protein:lipid ratio (lipid = cardiolipin)
Cardiolipin - unique phospholipid-also found in many bacterial membranes
IMM is very impermeable due to cardiolipin therefore channels & pumps are required to
move things across
o100 different proteins
oIncluding proteins of the ETC
3. Matrix
gel-like from high protein [ ]
contains DNA and ribosomes, tRNA
mitochondrial DNA encodes for 37 genes
However, mitochondrial function requires 3,000 proteins
Therefore, mitochondria function requires nuclear gene products, and these proteins must be
imported (targeted) to mitochondria
Posttranslational Uptake of Proteins Into Mitochondria
Mitochondria proteins are completely translated on free ribosomes in cytosol
What is the targeting sequence of mitochondrial proteins?
1. mitochondrial “presequence”
oat amino terminus of “preprotein”
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find more resources at oneclass.com
oseveral positively charged amino acids
oFor soluble matrix proteins
2. internal sequence & stop transfer sequence
ofor integral IMM proteins
To Enter Mitochondria:
Protein is first unfolded by HSP70 (chaperone protein)
Protein binds to its receptor on OMM
olocated next to a translocon on OMM
oTOM (translocon of outer membrane)
IMM integral proteins:
directed to TIM22 complex of IMM
TIM (Translocon of inner membrane)
stop transfer sequence embeds protein in the IMM
oincludes all the proteins of the ETC and the ATP synthase
Matrix proteins:
directed to TIM23 complex of IMM
preprotein moves through TIM because of membrane potential differences across IMM
associates with mtHSP70 which also helps pull it through
Once in matrix:
oassociates with HSP60
folds preprotein
omitochondrial processing peptidase (MPP) - a protease, that cuts off presequence to create
mature protein
Includes all the enzymes of the Kreb’s/citric acid cycle
How Does The Mitochondria Make ATP?
Start with Glucose (or amino acids, or glycerol and fatty acids)
1. Glycolysis – occurs in the cytosol
2. Krebs cycle/Citric Acid/TCA Cycle – occurs in the mitochondrial matrix
3. Electron Transport Chain – occurs in the Inner Mitochondrial Matrix
Total Result of Aerobic Respiration
C6H12O6 + 6O2 6C02 + 6H2O + 38 ATP
Chemical Reactions
Performed by enzymes (proteins)
oact on substrates (targets) to produce a chemical change in the substrate
ATP Production
1. Glycolysis
Glucose (6 C) - contains high energy electrons
first hydrolyzed into 2 molecules of pyruvate/pyruvic acid (3 C)
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find more resources at oneclass.com
involves 10 chemical reactions by enzymes
Pyruvic acid then moves into mitochondrial matrix through a special pyruvate transporter
It is converted to a 2 C molecule called acetyl coA
oone CO2 and one NADH are also generated
2. Kreb’s cycle
Acetyl coA – bound to a 4 C molecule oxaloacetate (OAA) to create citrate (6 C)
Citrate (6 C) converted back to OAA (4 C) during Kreb’s cycle
OAA then attached to an incoming Acetyl coA and cycle continues
Kreb’s cycle contain many enzymes for this conversion
Enzymes break down carbon molecules through “oxidation reactions”
oOxidation: loss of electrons
carbon molecules lose electrons
oelectrons are from hydrogen atoms in carbon molecules
NAD+ and FAD become reduced
oReduction: gain of electrons
oi.e. NAD+ becomes NADH
Net Result:
oCitrate (6 C) OAA (4 C)
By-products:
o3 NAD+ are reduced to NADH
o1 FAD is reduced to FADH2
o2 CO2 molecules are released
o1 GTP molecule is produced
High energy electrons in NADH and FADH2 are used to make ATP How?
1. Hydrogen atoms split into protons (H+) and electrons
2. Electrons are passed along ETC
3. Protons are pumped into intermembrane space
4. Proton gradient is used to make ATP
3. Electron Transport Chain (ETC)
consists of 4 IMM transmembrane complexes (contain proteins with prosthetic groups)
they oxidize NADH & FADH2 & take electrons
have the ability to accept electrons and donate them to the next protein complex
pass electrons from one complex to the next
final electron accepter is oxygen (becomes reduced)
oaccepts electrons and 2 protons from matrix to make water
these IMM complexes also have proteins which act as proton pumps
use the energy released from electron transfer to pump protons into the intermembrane space
Proton Gradient
a proton gradient develops in intermembrane space
ohigh [H+] = low pH
ocreates an electrochemical gradient across IMM
electrochemical gradient
creates a “proton-motive force”
Used by the ATP synthase to make ATP from ADP
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Mitochondria arose from phagocytosis of aerobic prokaryote can divide in the cell: mitochondrial fission . Functions: site of aerobic respiration, utilizing oxygen to extract energy from macromolecules (primarily glucose) and converting it to. Atp cells" energy source energy is released when atp is hydrolyzed to adp + pi. Many mitochondria in: muscle cells, liver cells, fat cells, plant cells & sperm cells. Parts of the mitochondria: outer mitochondrial membrane (omm) Contain porin proteins - large channels: bacterial protein. Cristae - many thin folds of imm to increase the surface area. Imm is 75% protein:lipid ratio (lipid = cardiolipin) Cardiolipin - unique phospholipid-also found in many bacterial membranes. Imm is very impermeable due to cardiolipin therefore channels & pumps are required to move things across: 100 different proteins, including proteins of the etc, matrix gel-like from high protein [ ] contains dna and ribosomes, trna. Therefore, mitochondria function requires nuclear gene products, and these proteins must be imported (targeted) to mitochondria.
