1. Mitochondria and respiratory chains SBS-922 Membrane Proteins John F. Allen School of Biological and Chemical Sciences, Queen Mary, University of London

2. http://jfa.bio.qmul.ac.uk/lectures

4. Why do mitochondria and chloroplasts have genome?

5. Typical prokaryotic (left) and eukaryotic (right) cells. W. Ford Doolittle Nature 392, 15-16, 1998

6. The endosymbiont hypothesis for the origin of mitochondria. W. Ford Doolittle Nature 392, 15-16, 1998

7. 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

8. Proposed solutions (hypotheses) There is no reason. “That’s 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. It’s all a question of hydrophobicity. The five-helix rule. (Anon) Some proteins (with co-factors) cannot be imported. (Anon) Co-location for Redox Regulation - CORR (Allen 1993, 2003 et seq.) Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?

9. BacteriumEndosymbiontBioenergetic organelle

10. 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, 19-38 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.

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

12. Redox regulation

14. IIIIIIIVATPase Mitochondrial matrix Inter-membrane space

15. IIIIIIIVATPase Mitochondrial matrix Inter-membrane space H+H+ H+H+ H+H+ H+H+ NADHO2O2 ATP ADP H2OH2O NAD + succinatefumarate

16. Redox regulation

17. Prediction Experimental (well, in silico…) results Persistence of “bacterial” redox signalling components in chloroplasts and mitochondria

20. "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. The mitochondrial theory of ageing

22. The mitochondrion is the worst imaginable place in the cell to keep genes. Whatever the reason for the persistence of mitochondrial genomes, it had better be a good one. Even without the Mitochondrial Theory of Ageing….

23. John Burn (Newcastle Institute of Clinical Genetics). Quoted in The Times, 9th September 2005 Mitochondria: – “…are not part of the genetic material that we consider makes us as human beings.” “My belief is that what we are doing is changing a battery that doesn’t work for one that does….Changing the mitochondria won’t affect the important DNA.” Coda. Two views of mitochondria View 1

24. Nick Lane. Power, Sex, Suicide. Mitochondria and the Meaning of Life. Oxford University Press. Publication: 27th October 2005. Mitochondria: – “…give striking new insights into why we are here at all, whether we are alone in the universe, why we have our sense of individuality, why we should make love, where we trace our ancestral roots, why we must age and die––in short, into the meaning of life.” Coda. Two views of mitochondria View 2