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

Molecular Biology of the Cell Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter Garland publishing. Lane N. Power, Sex, Suicide. Mitochondria and the Meaning of Life.Oxford University Press. October Allen JF.Allen JF. Power for life.Nature Oct 27;437(7063): Allen JF, Puthiyaveetil S, Strom J, Allen CA.Allen JF, Puthiyaveetil S, Strom J, Allen CA. Energy transduction anchors genes in organelles.Bioessays Apr;27(4): John C. Williams, Carolyn Sue, Graham S. Banting, Hua Yang, D. Moira Glerum, Wayne A. Hendrickson, and Eric A. Schon. Crystal Structure of Human SCO1 IMPLICATIONS FOR REDOX SIGNALING BY A MITOCHONDRIAL CYTOCHROME c OXIDASE “ASSEMBLY” PROTEIN. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 280, No. 15, Issue of April 15, pp –15211, 2005 Roxana Malpica, Bernardo Franco, Claudia Rodriguez, Ohsuk Kwon, and Dimitris Georgellis. Identification of a quinone-sensitive redox switch in the ArcB sensor kinase. PNAS September 7, 2004 vol. 101 no –13323 Chen YR, Chen CL, Zhang L, Green-Church KB, Zweier JL.Chen YR, Chen CL, Zhang L, Green-Church KB, Zweier JL. Superoxide generation from mitochondrial NADH dehydrogenase induces self inactivation with specific protein radical formation.J Biol Chem Sep 8; [Epub ahead of print] Bai Y, Park JS, Deng JH, Li Y, Hu P.Bai Y, Park JS, Deng JH, Li Y, Hu P. Restoration of mitochondrial function in cells with complex I deficiency.Ann N Y Acad Sci May;1042: References Nicholls DJ, Ferguson, SJ. Bioenergetics3. Academic Press/Elsevier Science 2002

– mitochondria power animal and plant cells – mitochondria are "domesticated" bacteria – during "domestication" - cell evolution - these bacteria relinquished many genes to the nucleus of the host cell....…and there are now few left (13 in the case of vertebrates, including mammals, including humans) encoding around 1 % of mitochondrial proteins And it is always the same 1 %..... Why? Mitochondria (singular; mitochondrion).

Scientific Art From Lane, N. (2005) Power, Sex, Suicide: Mitochondria and the Meaning of Life

Mighty Mitochondria copyright Odra Noel

A mitochondrion—one of many tiny power- houses within cells that control our lives in surprising ways copyright Ina Schuppe-Koistinen

Tomograph of rat liver mitochondrion C.A. Mannella, Wadsworth Center

This is a look inside an isolated mitochondrion, showing the outer membrane (OM), inner peripheral membrane (IM), and some of the internal compartments called cristae (C) formed by infolding of the inner membrane. Arrows point to narrow tubular regions of the IM that connect cristae to periphery and to each other.

Goodsell, D. S. The Machinery of Life. Springer-Verlag, New York and Berlin, 1993

Allen, J. F. (2003) Phil. Trans. R. Soc. B458, 19-38

IIIIIIIVATPase Mitochondrial matrix Inter-membrane space

Protein subunit encoded in mitochondrial DNA Protein subunit encoded in nuclear DNA Direction of vectorial proton translocation H+H+ Direction of electron transfer Mitochondrial inner membrane

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

Figure The path of electrons through the three respiratory enzyme complexes. The relative size and shape of each complex are shown. During the transfer of electrons from NADH to oxygen (red lines), ubiquinone and cytochrome c serve as mobile carriers that ferry electrons from one complex to the next. As indicated, protons are pumped across the membrane by each of the respiratory enzyme complexes. Molecular Biology of the Cell Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. 2002

"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

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

Nick Lane. Power, Sex, Suicide. Mitochondria and the Meaning of Life. Oxford University Press. Publication: 27th October 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