Cell Biology and Developmental Genetics

Lectures by

John F. Allen
School of Biological and Chemical Sciences, Queen Mary, University of London

jfallen.org

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

Cell Biology and Developmental Genetics

Lectures by John F. Allen

Slides and supplementary information:

jfallen.org/lectures

Lecture 4

Why do chloroplasts and mitochondria have genomes?

Inter-membrane space

II

III

IV

ATPase

Mitochondrial matrix

Thylakoid lumen

Photosystem II

Cyt b6-f

Photosystem I

ATPase

RubisCO

Chloroplast stroma

Problem Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?
Why do mitochondria and chloroplasts require their own separate 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 of mitochondrial and chloroplast genomes would provide the answer has proved unfounded. We cannot think of compelling reasons why the proteins made in mitochondria and 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

Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?

Proposed solutions (hypotheses)
There is no reason. Thats just how it is. (Anon) The Lock-in hypothesis. (Bogorad, 1975). In order for core components of multisubunit 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 when something 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)

Thermus thermophilus Complex I - coloured to distinguish subunits

Graphics by Wilson de Paula from 3m9s.pdb

Problem

Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?

Why do mitochondria and chloroplasts require their own separate 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 of mitochondrial and chloroplast genomes would provide the answer has proved unfounded. We cannot think of compelling reasons why the proteins made in mitochondria and chloroplasts should be made there rather than in the cytosol. At one time, it was suggested that some proteins have to be made in the organelle because they are too hydrophobic to get to their site in the membrane from the cytosol. More recent studies, however, make this explanation implausible. In many cases, 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 and London: Garland Science; 2007

Proposed solution (hypothesis)

Why Mitochondria and Chloroplasts Have Their Own Genetic Systems

Co-location for Redox Regulation - CORR
Vectorial electron and proton transfer exerts regulatory control over expression of genes encoding proteins directly involved in, or affecting, redox poise. This regulatory coupling requires co-location of such genes with their gene 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.
Allen, J. F. (1993) J. Theor. Biol. 165, 609-631

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

Bioenergetic organelle Endosymbiont Bacterium

Co-location for Redox Regulation - CoRR

Ten assumptions, axioms, principles jfallen.org/corr 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 and assembly into a functional, mature form. 4. Direct redox control of expression of certain genes was present in the bacterial progenitors of chloroplasts and mitochondria, and was vital for cell function before, during, and after the transition 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 retained and expressed only within the organelle. 6. For each bacterial gene that survives and is not under redox control, it is selectively advantageous for that gene to be located in the nucleus and expressed only in the nucleus and cytosol. If the mature gene product functions in chloroplasts or mitochondria, the gene is first expressed in the form of a precursor for import. 7. For any species, the distribution of genes between organelle and nucleus is the result of selective forces that continue to operate. 8. Those genes for which redox control is always vital to cell function have gene products involved in, or closely connected with, primary electron transfer. These genes are always contained within the organelle. 9. Genes whose products contribute to the organelle genetic system itself, or whose products are associated with secondary events in energy transduction, may be contained in the organelle in one group of organisms, but not in another. 10. Components of the redox-signalling pathways upon which co-location for redox regulation depends are themselves not involved in primary electron transfer, and so their genes have

Co-location for Redox Regulation - CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidative phosphorylation between mitochondria and the cell nucleus Prediction: Experimental results
Redox control of mitochondrial and chloroplast gene expression

Prediction: Experimental results

Persistence of bacterial redox signalling components in chloroplasts and mitochondria

Co-location for Redox Regulation - CoRR

Prediction Explanation of previous knowledge Distribution of genes for components of oxidative phosphorylation between mitochondria and the cell nucleus

Redox regulation

Nucleus

Cytosol

O2

N-phase

H2O

Mitochondrial matrix

Redox regulation

Inter-membrane space

II

III

IV

ATPase

Mitochondrial matrix

Inter-membrane space

I
H+

II

III
H+

IV
H+

ATPase

H+

NADH

O2

H2O

NAD+

succinate

fumarate

ADP

ATP

Mitochondrial matrix

Nucleus

Cytosol

O2

N-phase

H2O

Mitochondrial matrix

Redox regulation

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

Co-location for Redox Regulation CORR

Prediction Explanation of previous knowledge Distribution of genes for components of photosynthetic phosphorylation between chloroplasts and the cell nucleus

Redox regulation

Nucleus

Cytosol

Light

Light

CH2O
N-phase

Chloroplast stroma

CO2
Redox regulation

Thylakoid lumen

Photosystem II

Cyt b6-f

Photosystem I

ATPase

RubisCO

Chloroplast stroma

Thylakoid lumen

Photosystem II
O2

Cyt b6-f
H+

Photosystem I
H+

ATPase

H2O

H+

H+

NADP+ ADP H2O O2

H+ H+

NADPH ATP

H+

NADP+

RubisCO

ADP

NADPH Chloroplast stroma

ATP

Nucleus

Cytosol

Light

Light

CH2O
N-phase

Chloroplast stroma

CO2
Redox regulation

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

Co-location for Redox Regulation - CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidative phosphorylation between mitochondria and the cell nucleus Prediction: Experimental results
Redox control of mitochondrial and chloroplast gene expression

Prediction: Experimental results

Persistence of bacterial redox signalling components in chloroplasts and mitochondria

Lecture 5

Co-location for Redox Regulation