Class Mitochondria I

CELLULAR
ENERGETICS

Prof. Lilian Spencer

Cristae
Inner membrane
Outer
membrane
 Mitochondria

- Mitochondria occupy much of the cell volume (25%)

- When Glucose is converted into Pyruvate by Glycolysis, only a small fraction
of the total free energy is potentially allowed to release.

In the Mitochondria (Mit) The metabolism of sugars is complete:

Pyruvate is imported into the Mit. and oxidized by O2 to CO2 + H2O.
This allows 15 times more ATP than in the product of glycolysis.

Structure
Mitochondria External Membrane (EM)

Internal Membrane(IM)

2 Internal compartments Matrix

Intermembrane Space

EM: Carrier proteins Porin Prot. channels

(5.000 Dalton)
EM: External Membrane
Internal Membrane (IM)

• Highly specific

• Phospholipids: Cardiolipin Helps the impermeability of the IM.

• Enzymes in the respiratory chain (F0F1 ) Oxidative phosphorylation

• Presents Cristaens: increases the surface area of IM ATP

Matrix: Metabolism of Pyruvate and Fatty Acids

Cycle of Citric Acid (Krebs) Acetil CoA

Oxidation

CO2 + NADH e- Source Respiratory Chain

Oxidative Phosphorylation

ATP
Fig. 14-8 : General Organization of Mitochondria
Matrix

M. internal

M. external

Intermembranous
space

A chemosmotic process is performed because it converts Oxidation Energy

into ATP (Oxidative Phosphorylation).

Chemi-osmotic process: It is the common pathway used by the Mitochondria

in eukaryotes to harness energy in biological purposes.

Chemiosmotic Generation of ATP(Chemi)

Process of membrane transport (Osmotic).
 DNA from the mitochondria

• Evidence exp. Common ancestor with bacteria. Mitochondria maintain a circular DNA
for essential organelle proteins.

Mitochondrial DNA genes have cytoplasmic inheritance:

• In yeast the inheritance Mit. It depends on the two parents.

•In mammals the spermatozoid has very little cytoplasm and almost all mitochondria of
the embryo are derived from the ovule.

•Studies with mice show that 99.99% of DNA Mit is inherited from the mother and 0.01%
from the father.

DNA Mit + ribosoma Mit Mit. Essential Proteins

(Sub-units of the multimeric complexes of
Transport of e- ). ATPsynthase
RNA polymerase and mitochondrial DNA polymerase are synthesized in the cytosol and
imported into mitochondria.

Biogenesis of organelles: Mitochondria

The process of targeting the newly synthesized polypeptide to its final destination.
Fig. 17-1: Distribution of the proteins encoded by the nucleus in the eukaryotic cell

N-terminal
The majority of mitochondrial proteins are synthesized in the cytosol

Freshly made proteins

They are oriented to the organelles

Recognition of the uptake-orientation sequence.

Consecutive action of 2 membrane-bound receptor systems.

• Orientation of the protein to the organelle.

• the sequence of protein is directed to the compartment in the organelle.
Table 17-1 y 17-2: Examples of mitochondrial proteins that are synthesized in the cytosol

Pulse and follow-up (pulse and hunt) experiments (Labelled with tritiated
methionine)

• Most of the proteins imported into the mit. They originate as N-terminal
precursors.
• Precursor presents one or more guiding sequences
Endosymbiont Hypothesis Ancestral eukaryotic cell
Fig. 16-2: Membrane orientation and the direction of proton movement during
chemiosmotically coupled ATP synthesis in bacteria, mitochondria, and
chloroplasts.
 Cellular Energy: (Energy Plant)

Molecule captured and transfer E into ATP: Adenosine triphosphate

hydrolysis
ATP ADP + Pi - 7.3 Kcal/mol

Generation of ATP from ADP + Pi (Endergonic reaction)

Pi-2 + H+ + ADP -3 ATP-4 + H2O

The energy (E) comes from Aerobic Oxidation of Fatty Acids, and Hexoses
(Glucose) CO2 + H2O

- Initial steps for the oxidation of glucose is Glycolysis and occurs in the
cytosol
- The final steps require O2, generate most of ATP and take place in
mitochondria.
Fig. 16-1: Chemi-osmotic coupling.

(Proton -motive Force) Boosts ATP system

Proton - Motive Force: The energy source that drives the synthesis of ATP and is in the
transmembrane gradient of [H +] and the electric potential.

It is generated by the gradual movement of e- from a high energy state to a lower E, through
e- transporters in the mitochondrial membrane
Eukaryotes are obligate aerobes: they grow only in the presence of oxygen and
metabolize glucose.

Anaerobic degradation of glucose, called fermentation, is the basis of

beer and wine production.

During the prolonged contraction of mammalian skeletal muscle cells, when

oxygen becomes limited, muscle cells ferment glucose to two molecules of lactic
acid—again, with the net production of only two molecules of ATP per glucose
molecule.

vs

Pyruvate formed in glycolysis is transported into mitochondria, where it is oxidized

by O2 to CO2 in a series of oxidation reactions collectively termed cellular
respiration.
FIGURE 8-5 Anaerobic versus aerobic
metabolism of glucose
 Classes of membrane proteins:

• F0F1 Complex or ATP synthase (ATP-powered F-class proteomic pump).

The e- flow creates an electrochemical gradient of H+ or Proton-motive force, which

propels the synthesis of ATP

Aerobic Oxidative Phosphorylation.

“Oxidation of glucose and Fatty acids to CO2 "coupled to the synthesis of up to 36

molecules of ATP

C6H12O6 + 6CO2 + 36Pi-2 + 36 ADP + 36 H+ 6CO2 + 36 ATP + 42 H2O

 Glycolysis Initial stage of glucose metabolism,
Occurs in the cytosol and does not intervene O2
Produces small quantities of ATP

Piruvate (3C)

Transported to the mitochondria

MIT: Pyruvate is oxidized by O2 CO2

Chemo-osmotic coupling

ATP

-Cytosolic enzymes convert glucose into pyruvate:

10 Ez

GLUCOSE “2 PYRUVATE: Glycolytic pathway

 - All intermediates between glucose and pyruvate are phosphorylated
compounds

- Form 4 ATP from ADP Final yield 2ATP

Glucolysis

- 2 ATP are consumed

Chemical Equation:

=O
=O
C6H12O6 2CH3- C – C – OH + 4 H+ + 4 e-

Transferred to NAD +
(Nicotinamide dinucleotide)

(oxi) (red)

2H+ + 4e- + 2NAD+ 2NADH

Nicotinamide adenine dinucleotide

Fig. 16-3: Glucolytic pathway

Produced ATP by phosphorylation

at the substrate level
 General Reaction of Glucolysis

C6H12O6 + 2NAD+ + 2ADP + 2 Pi 2C3H4O3 + 2NADH + 2ATP

Produced by
phosphorylation
4ATP 2ATP Final yield at the substrate
level

Generated

The remaining 34 ATP molecules Aerobic glucose metabolism

Mitochondria have 2 different membranes from the structural and functional point of
view:

Transport (mit)
Pyruvate CO2 + 34 ATP / 36 ATP Of glucose CO2
Characteristics of the Mitochondria

•Ext Membrane: PORIN Channel Ion passage and small molecules.

•Internal Membrane: Permeable barrier between the cytosol < 5000 Dalton and the Mit.
Matrix

Contains : - F0F1 Complex where ATP is synthesized

- Transport of e- to the O2 from NADH or FADH2 (nicotinamide adenine
dinucleotide hydride and flavin dinucleotide)

Carrier Prot. E.g. Cardiolipin (difosfaditil glicerol) is

an internal membrane lipid Reduces the permeability of H + (protons)

A Proton-Motive Force is generated

 Fig 16-7: Diagram of the longitudinal section of the Mitochondria.

D
A

C granules Please, Explain the figure

Fig. 16-8: FAD+ (Flavin dinin dinucleotide) structure and its reduction to FADH2.
 Pyruvate and Fatty Acids CO2 + H2O

Coupling of ATP from ADP + Pi

They can be divided into 3 reactions.

1- Oxidation of Pyruvate and Fatty Acids CO2 + H2O

Coupled the reaction of the coenzymes NAD+ and FAD+ to NADH and FADH2 this
occurs in the matrix

2.- Transfer of e- from NADH or FADH2 to O2

It is produced in the inner membrane and are coupled to the generation of a
proton-motive force.

3.- Use of energy stored in the electrochemical gradient of (H +) protons, for

the synthesis of ATP in the F0F1 complex of the IM.

-IM forms cristaes to increase surface area and increase the ability to form
ATP
Fig. 16-9: Summary of Aerobic Oxidation of Pyruvate in Mitochondria. The ext
memb is not included.
Remember
“Mitochondrial oxidation of Pyruvate begins with the formation of Acetyl CoA”.

IM Pyruvate
Dehydrogenase (Enzyme complex)
Pyruvate CoA CO2 ΔG = -8Kcal/mol
(citosol) Mitochondrial matrix

Fig: 16-10: Structure of Acetyl CoA

LOOK THE GLYCOLYSIS AND KREBS CYCLE PROCESS
Fig. 16-14: Oxidation of
Fatty Acids in Mitochondria
Summary of aerobic oxidation of glucose and fatty acids:
Stage I: In cytosol, glucose is converted to pyruvate and fatty acid to fatty CoA
Stage II: In the matrix, pyruvate and fatty acyl CoA are conveted to acetyl CoA
Stage III: electron transport and generates a proto-motive force
Stage VI: ATP synthase to synthesize ATP (matrix)
https://www.youtube.com/watch?v=mxbodI60OT4

Next Class

Cellular Respiration or Electronic chain

See next video

https://www.youtube.com/watch?v=vlbWdMphYEI
Discussion of Class
activity of mitochondia
 Class of mitochondria II

Based on the article review by Al Mir and

Therry
1- What is the main idea of the article?.

2- According to this article, what are the

functions of the mitochondria?
Any Question?