Mitochondria and respiratory chains

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SBCS-922 Membrane Proteins
Mitochondria and respiratory chains
John F. Allen School of Biological and Chemical
Sciences, Queen Mary, University of London
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Complex II structure.... and location of genes
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The Respiratory Chain Includes Three Large Enzyme
Complexes Embedded in the Inner
Membrane Molecular Biology of the Cell Bruce
Alberts, Alexander Johnson, Julian Lewis, Martin
Raff, Keith Roberts, and Peter Walter. 2002
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Not forgetting complex II
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Huang, L.,  Sun, G.,  Cobessi, D.,  Wang,
A.C.,  Shen, J.T.,  Tung, E.Y.,  Anderson,
V.E.,  Berry, E.A. (2006) 3-Nitropropionic Acid
Is a Suicide Inhibitor of Mitochondrial
Respiration That, upon Oxidation by Complex II,
Forms a Covalent Adduct with a Catalytic Base
Arginine in the Active Site of the Enzyme
J.Biol.Chem. 281 5965-5972
http//www.jbc.org/cgi/content/full/281/9/5965
Abstract We report three new structures of
mitochondrial respiratory Complex II (succinate
ubiquinone oxidoreductase, E.C. 1.3.5.1 EC ) at
up to 2.1 Å resolution, with various inhibitors.
The structures define the conformation of the
bound inhibitors and suggest the residues
involved in substrate binding and catalysis at
the dicarboxylate site. In particular they
support the role of Arg297 as a general base
catalyst accepting a proton in the
dehydrogenation of succinate. The dicarboxylate
ligand in oxaloacetate-containing crystals
appears to be the same as that reported for
Shewanella flavocytochrome c treated with
fumarate. The plant and fungal toxin
3-nitropropionic acid, an irreversible
inactivator of succinate dehydrogenase, forms a
covalent adduct with the side chain of Arg297.
The modification eliminates a trypsin cleavage
site in the flavoprotein, and tandem mass
spectroscopic analysis of the new fragment shows
the mass of Arg297 to be increased by 83 Da and
to have the potential of losing 44 Da, consistent
with decarboxylation, during fragmentation.
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(By Richard Wheeler (Zephyris) 2006. PDB1YQ3
Licensing GFDL-self CategoryProtein
images )
http//en.wikipedia.org/wiki/ImageSuccinate_Dehyd
rogenase_1YQ3_Electron_Carriers_Labeled.png
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Protein subunit encoded in mitochondrial DNA
Protein subunit encoded in nuclear DNA
Mitochondrial inner membrane
Direction of vectorial proton translocation
Direction of electron transfer
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Inter-membrane space
I
II
III
IV
ATPase
H
H
NADH
O2
H2O
ADP
NAD
succinate
fumarate
ATP
Mitochondrial matrix
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Figure 14-59 Comparison of mitochondrial
genomes. Less complex mitochondrial genomes
encode subsets of the proteins and ribosomal RNAs
that are encoded by larger mitochondrial genomes.
There are only four genes present in all known
mitochondrial genomes these encode ribosomal
RNAs (rns and rnl), cytochrome b (cob), and a
cytochrome oxidase subunit (cox1). (Adapted from
M.W. Gray et al., Science 2831476-1481, 1999.
With permission from AAAS.)
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The mitochondrial theory of ageing
"Errors" in electron transfer - transfers to the
"wrong" electron acceptor - occur at fixed
frequency. The products of these reactions
damage mitochondrial genes, which then produce
defective proteins, which then make more "errors"
in electron transfer....damaging more genes,
making more defective proteins....and so on.
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ESCOBAR GALVIS, M L, ALLEN, J F and HÅKANSSON, G
(1998) Protein synthesis by isolated pea
mitochondria is dependent on the activity of
respiratory complex II Current Genetics 33,
320-329 In isolated pea (Pisum sativum L.)
mitochondria incorporation of 35S-methionine into
newly synthesised proteins was influenced by the
presence of site-specific inhibitors of the
respiratory electron transport chain. These
effects were not produced by changes in the rate
of respiratory electron transport itself nor by
changes in ATP concentration. Protein synthesis
was inhibited by inhibitors of ubiquione
reduction but not by inhibitors of ubiquinol
oxidation. By the use of additional inhibitors at
specific sites of the respiratory chain,
different oxidation-reduction states were
obtained for the different complexes in the
electron transport chain. It was found that
electron transport through succinateubiquinone
oxidoreductase (respiratory complex II) was
specifically required for protein synthesis, even
when all the other conditions far protein
synthesis were satisfied. We suggest that a
subunit of complex II, or a component closely
associated with complex II, is involved in a
regulatory system that couples electron transport
to protein synthesis.
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The Respiratory Chain Includes Three Large Enzyme
Complexes Embedded in the Inner
Membrane Molecular Biology of the Cell Bruce
Alberts, Alexander Johnson, Julian Lewis, Martin
Raff, Keith Roberts, and Peter Walter. 2002
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• Complex III. Structure and Function.

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Thank you for listening
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SBCS-922 Membrane Proteins
Mitochondria and respiratory chains
John F. Allen School of Biological and Chemical
Sciences, Queen Mary, University of London
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