Oxidative phosphorylation

NADH transportOxidative phosphorylation

p691

Only those with specific transporters can pass

All pathways related to fuel oxidation except glycolysis

N side

Oxidative phosphorylation

• Converting the energy from electrons (from NADH and FADH2) to ATP

1. NAD+

2. FAD3. Ubiquinone4. Cytochromes5. Iron-sulfur proteins

Five electron carrying molecules

Ubiquinone (coenzyme Q; Q; Q10)

UbiquinonePlastoquinone (plant chloroplast)Menaquinone (bacteria)

p693

p694cytochromes

p695

Iron-sulfur proteins

Method for determining the sequence of electron carriers

p696

A B C D E F

A B C D E F

A B C D E F

p698

Chemical uncouplers• Chemicals like DNP

and FCCP are weak acid with hydrophobic properties that permit them to diffuse readily across mitochondrial membranes. After entering the matrix in the protonated form, they can release a proton, thus disspating the proton gradient.

p707

Ionophores

• Valinomycin (an ionophore) allows inorganic ions to pass easily through membranes. This will uncouple electron transfer from oxidative phosphorylation.

p406

p696

p698Complex I

p697

Complex I & II

p700Complex III

p702Complex IV

H+H+H+H+H+H+H+H+H+H+H+H+

III

Cyt cCyt c

H+H+H+H+

III

IV

NADH

NAD+

e

e

Qee

H+H+OH2OH2O

NADH

FADH2

eFAD

e

H+H+O

FADH2

Mitochondrial inner membrane

Mitochondrial matrix

Mitochondrial intermembrane

space

p703

p675

p711Mitochondrial ATP synthase complex

p687Oxidative phosphorylation in brown fat tissue is uncoupled with ATP synthesis

p718Regulation

NADH transport

• NADH produced by glycolysis must be transported into mitochondria to produce ATP.

• However, NADH cannot enter mitochondria directly. Instead it is transported by the form of malate or glycerol 3-phosphate.

Aspartate

p715Malate-aspartate shuttle

NADH

NAD+

OAA

malateMalate

dehydrogenase

NAD+

NADHOAA

Glutamate

-KG

Malate dehydrogenase

Aspartate aminotransferase

Aspartate aminotransferase

NAD+Glycerol 3-phosphate

p715Glycerol 3-phosphate shuttleNADH

DHAP

DHAP

FAD

FADH2

Q

Cytosolic glycerol 3-phosphate

dehydrogenase

Glycolysis

III

NADHGlc G6P F6P F1,6BP G3P

DHAP

1,3BPG 3-PGA 2-PGA PEP Pyruvate

NADH

NADHFADH2

NADH

Malate-aspartate

shuttle

Glycerol 3-phosphate

shuttle

p720Mitochondrial genome

p35

Mitochondrion is probably evolved from endosymbiotic bacteria

Mitochondrial encephalomyopathies

• Mutations in mitochondrial genes cause mitochondrial encephalomyopathies that affecting primarily the brain and skeletal muscle. Because infants inherit their mitochondria from their mothers, so mitochondrial encephalomyopathies are maternal-linked.

Leber’s hereditary optic neuropathy (LHON)

• LHON is the result of defective mitochondrial genes that are involved in electron transfer.

• Vision loss usually occurs between the ages of 15 and 35.

Myoclonic epilepsy and ragged-red fiber disease (MERRF)

• Mutation in the mitochondrial gene that encodes a tRNA specific for lysine (lysyl-tRNA) results in MERRF.

• Synthesis of several proteins require this tRNA is interrupted.

p720

MERRF

• MERRF patients often have abnormally shaped mitochondria containing paracrystalline structures.

• This lysyl-tRNA mutation is also one of the causes of adult-onset (type II) diabetes.

Many respriatory proteins are encoded by mitochondria

Bacteria do have respiratory chain enzymes

• For example, E. coli has NAD-linked electron transfer from substrate to O2, coupled to the phosphorylation of cytosolic ADP.

Mitochondria, apoptosis, and oxidative stress

Mitochondria is not only involved in ATP synthesis. It is also involved

in cellular damage and death.

The role of mitochondria in apoptosis

• When cell receives a signal for apoptosis, one consequence is the permeability of the outer mitochondrial membrane will increase, allowing cytochrome c release.

• The release of cytochrome c will activate caspase 9, which will initiate the protein degradation process.

Mitochondria can produce superoxide free radical