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Lectures by

John F. Allen

School of Biological and Chemical Sciences, Queen Mary, University of London

Cell Biology and Developmental Genetics

1

jfallen.org

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Cell Biology and Developmental Genetics

Lectures by John F. Allen

Endosymbiosis and the origin of bioenergetic organelles. Some history

Endosymbiosis and the origin of bioenergetic organelles.

A modern view

Mitochondria as we know them and don't know them

Why do chloroplasts and mitochondria have genomes?

Co-location for Redox Regulation

Mitochondria, ageing, and sex energy versus fidelity

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Cell Biology and Developmental Genetics

Lectures by John F. Allen

Slides and supplementary information:

jfallen.org/lectures

http://jfallen.org/lectures/http://jfallen.org/lectures/

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Why do chloroplasts and mitochondria have

genomes?

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I II III IV ATPase

Mitochondrial matrix

Inter-membrane space

Th l k id l

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Thylakoid lumen

Cyt b6-f Photosystem I ATPasePhotosystem II

RubisCO

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Problem

Why Do Mitochondria and Chloroplasts Have TheirOwn Genetic Systems?

Why do mitochondria and chloroplasts require their ownseparate genetic systems when other organelles that share

the same cytoplasm, such as peroxisomes and lysosomes,do not? . The reason for such a costly arrangement is not

clear, and the hope that the nucleotide sequences ofmitochondrial and chloroplast genomes would provide the

answer has proved unfounded. We cannot think of

compelling reasons why the proteins made in mitochondriaand chloroplasts should be made there rather than in the

cytosol.

Molecular Biology of the Cell 1994 Bruce Alberts, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts, and James D. Watson

Molecular Biology of the Cell, 3rd edn. Garland Publishing

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Proposed solutions (hypotheses)

There is no reason. Thats just how it is. (Anon)

The Lock-in hypothesis. (Bogorad, 1975). In order for core components ofmultisubunit complexes to be synthesised, de novo, in the correct compartment.

The evolutionary process of transfer of genes from organelle to nucleus is still

incomplete.E.g. Herrmann and Westhoff, 2001: The partite plant genome is not in a phylogenetic

equilibrium. All available data suggest that the ultimate aim of genome restructuring in

the plant cell, as in the eukaryotic cell in general, is the elimination of genome

compartmentation while retaining physiological compartmentation.

The frozen accident. The evolutionary process of gene transfer was underway whensomething happened that stopped it. E.g. von Heijne, 1986.

Its all a question of hydrophobicity. The five-helix rule. (Anon)

Some proteins (with co-factors) cannot be imported. (Anon)

- -

Why Do Mitochondria and Chloroplasts Have TheirOwn Genetic Systems?

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Thermus thermophilusComplex I - coloured to

distinguish subunits

Graphics by Wilson dePaulafrom 3m9s.pdb

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Why do mitochondria and chloroplasts require their own separate genetic systemswhen other organelles that share the same cytoplasm, such as peroxisomes andlysosomes, do not? . The reason for such a costly arrangement is not clear, and the

hope that the nucleotide sequences of mitochondrial and chloroplast genomes wouldprovide the answer has proved unfounded. We cannot think of compelling reasonswhy the proteins made in mitochondria and chloroplasts should be made there ratherthan in the cytosol.

At one time, it was suggested that some proteins have to be made in the organellebecause they are too hydrophobic to get to their site in the membrane from thecytosol. More recent studies, however, make this explanation implausible. In manycases, even highly hydrophobic subunits are synthesized in the cytosol.

Molecular Biology of the Cell

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P Molecular Biology of the Cell. Fifth Edition. New York andLondon: Garland Science; 2007

Problem

Why Do Mitochondria and Chloroplasts Have

Their Own Genetic Systems?

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Proposed solution (hypothesis)

Why Mitochondria and Chloroplasts Have Their Own

Genetic Systems

Allen, J. F. (1993) J. Theor. Biol. 165, 609-631

Allen, J. F. (2003) Phil. Trans. R. Soc. B458, 19-

Co-location forRedoxRegulation - CORR

Vectorial electron and proton transfer exerts regulatory control over

expression of genes encoding proteins directly involved in, oraffecting, redox poise.

This regulatory coupling requires co-location of such genes with theirgene products; is indispensable; and operated continuously

throughout the transition from prokaryote to eukaryotic organelle.

Organelles make their own decisions on the basis of environmental

changes affecting redox state.

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BacteriumEndosymbiontBioenergetic organelle

Co location for Redox Regulation CoRR

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1. As now generally agreed, bioenergetic organelles evolved from free-living bacteria.2. Gene transfer between the symbiont or organelle and the nucleus may occur in either direction

and is not selective for particular genes.

3. There is no barrier to the successful import of any precursor protein, nor to its processing andassembly into a functional, mature form.

4. Direct redox control of expression of certain genes was present in the bacterial progenitors ofchloroplasts and mitochondria, and was vital for cell function before, during, and after thetransition from bacterium to organelle. The mechanisms of this control have been conserved.

5. For each gene under redox control, it is selectively advantageous for that gene to be retainedand expressed only within the organelle.

6. For each bacterial gene that survives and is not under redox control, it is selectivelyadvantageous for that gene to be located in the nucleus and expressed only in the nucleusand cytosol. If the mature gene product functions in chloroplasts or mitochondria, the gene isfirst expressed in the form of a precursor for import.

7. For any species, the distribution of genes between organelle and nucleus is the result ofselective forces that continue to operate.

8. Those genes for which redox control is always vital to cell function have gene products involvedin, or closely connected with, primary electron transfer. These genes are always containedwithin the organelle.

9. Genes whose products contribute to the organelle genetic system itself, or whose products areassociated with secondary events in energy transduction, may be contained in the organellein one group of organisms, but not in another.

10. Components of the redox-signalling pathways upon which co-location for redox regulationdepends are themselves not involved in primary electron transfer, and so their genes have

Co-locationfor RedoxRegulation-CoRRTen assumptions, axioms, principles jfallen.org/corr

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Co-locationfor RedoxRegulation-CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidativephosphorylation between mitochondria and the cell

nucleus

Prediction: Experimental results

Redox control of mitochondrial and chloroplast geneexpression

Prediction: Experimental results

Persistence of bacterial redox signalling components

in chloroplasts and mitochondria

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Co-locationfor RedoxRegulation-CoRR

Prediction

Explanation of previous knowledge

Distribution of genes for components of oxidativephosphorylation between mitochondria and the cell

nucleus

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Redox regulation

Nucleus Cytosol

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Redox regulation

N-phase

Mitochondrial matrix

O2

H2O

Inter-membrane space

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I II III IV ATPase

Mitochondrial matrix

Inter membrane space

Inter-membrane space

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I II III IV ATPase

Mitochondrial matrix

Inter membrane space

H+ H+ H+

H+

NADH O2

ATP

ADP

H2O

NAD+ succinate fumarate

Nucleus Cytosol

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Redox regulation

N-phase

Mitochondrial matrix

O2

H2O

Allen JF (2003) The function of genomes in bioenergetic organellesPhilosophical Transactions of the Royal Society of London Series B-Biological Sciences 358: 19-37

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Co-locationfor RedoxRegulation-CORR

Prediction

Explanation of previous knowledge

Distribution of genes for components ofphotosynthetic phosphorylation between

chloroplasts and the cell nucleus

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Redox regulation

Nucleus Cytosol

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Redox regulation

Light Light

N-phase

Chloroplast stroma

CO2

CH2O

Thylakoid lumen

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Chloroplast stroma

Cyt b6-f Photosystem I ATPasePhotosystem II

RubisCO

Thylakoid lumen

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Cyt b6-f Photosystem I ATPase

Chloroplast stroma

Photosystem II

RubisCO

H+H+ H+

H

ATP

NADP+

O2

H2O

H+H+

H+

ADP

NADPH

ATP

ADP

H2O O2

NADP+

NADPH

Nucleus Cytosol

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Redox regulation

Light Light

N-phase

Chloroplast stroma

CO2

CH2O

Allen JF (2003) The function of genomes in bioenergetic organellesPhilosophical Transactions of the Royal Society of London Series B-Biological Sciences 358: 19-37

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Co-locationfor RedoxRegulation-CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidativephosphorylation between mitochondria and the cell

nucleus

Prediction: Experimental results

Redox control of mitochondrial and chloroplast geneexpression

Prediction: Experimental results

Persistence of bacterial redox signalling components

in chloroplasts and mitochondria

Lecture 5

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Lecture 5

Co-location for Redox Regulation