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Power, Sex, Suicide: Mitochondria and the Meaning of Life

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    The mother of inventions Nick Lane s Power, Sex, Suicide attempts to show that there is more to life than DNA. Steven Rose follows the trail * Buzz up!
    Message 1 of 1 , Dec 1, 2009
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      The mother of inventions

      Nick Lane's Power, Sex, Suicide attempts to show that there is more to life than DNA. Steven Rose follows the trail

      Power, Sex, Suicide: Mitochondria and the Meaning of Life
      by Nick Lane
      348pp, Oxford, £18.99

      Power, sex, suicide; the words evoke blood and thunder, whodunit territory. But then that subtitle. The last bit is clear enough, but mitochondria? If you've got biology at GCSE you might just remember that these are the tiny sausage-shaped structures packed into every living cell and generally glibly referred to as the cellular "powerhouse" - the site of its major energy-generating systems. That might link them to power, but how about the rest? Could we be into fashionable forensics?

      Perhaps sadly, no. Nick Lane is a biochemist and his book devotedly plots the latest findings and controversies in a field whose protagonists have exasperatedly - if also affectionately - long been known as mitochondriacs by their less committed colleagues. In a world where popular accounts of biology seem exclusively concerned with genetics, Lane's ambition is to convince the rest of us that there is more to life than DNA - or at least that portion of the cell's DNA locked up in its nucleus and which, for our species, has been laboriously sequenced in the Human Genome Project.

      What atoms are to physicists, cells are to biologists: the units, 100th to a 10th of a millimetre in diameter, of which all living creatures are composed. We owe the term - by analogy to monk's cells in a monastery - to the 19th-century microscopists who identified them and later found that each contained a small round structure embedded within it: the nucleus. Surrounding the nucleus was what was initially assumed to be a clear gel, which was named protoplasm. It wasn't until the development of higher powered light and then electron microscopes that the "protoplasm" turned out to be traversed by complex membranes and packed with granules, among them the mitochondria, generally about 300 to 400 per cell, although some can contain 10 times more. By the 1950s, there were techniques for smashing the cells and centrifuging out their separate components to study in isolation, and mitochondriology came of age.

      All creatures require energy to survive, and most of us obtain that energy by the slow burning of carbohydrates and fats, oxidising them to carbon dioxide and water. The energy released by this burning is used to synthesise a small molecule, known as ATP, a sort of "energy currency" which can then in turn be traded in for the multitude of cellular needs, from building proteins to contracting muscles or transmitting signals down nerves. Oxidising sugars, and coupling that oxidation to the synthesis of ATP, is what most of us older biochemists were taught that mitochondria are about, although it took many years, ingenious experiments and much quite savage controversy before the extraordinary mechanism for such synthesis won the rich and eccentric biochemist Peter Mitchell his Nobel prize in 1978. Lane tells the story of that discovery in all its excruciating detail.

      But although this is where older biochemical stories (including my own Chemistry of Life) would have started and even ended, it is not where Lane begins, and for a fascinating reason. Except in bacteria, which don't have one, nearly all the cell's DNA is in the nucleus, packed into chromosomes. But it turns out that there is residual DNA in the mitochondria as well, some 13 genes-worth, coding for some, though far from all, of the mitochondrial proteins. Why? In 1967 Lynn Margulis proposed the initially scandalous but now universally accepted hypothesis that dominates Lane's early chapters. The consensus among biologists is that in life's early days, 3.5 billion years ago, many and varied forms of single celled organisms floated in a thin soup of abiotically synthesised chemicals, perhaps in the vicinity of drying seas, thermal vents or volcanoes, deriving their energy from where they could grab it. Margulis argued that mitochondria were originally free-living organisms, which became engulfed by other cells, which, themselves lacking the mitochondrial capacity to oxidise, struck a different bargain. Instead of eating the creatures they swallowed, they used the mitochondria to perform the chemical transformations needed to derive the maximum energy from their other foodstuffs.

      The mitochondria sacrificed their own individuality, but the combined - symbiotic - cells were so efficient that they out-reproduced most other life forms and became the basic stock from which all today's multicellular organisms evolved.

      Single celled organisms can reproduce by budding; most multicellular forms use sex, in which two cells merge and shuffle their genes. But for this to occur, the merged cell also requires energy, which comes from the mitochondria. So in sex, one cell, the sperm, is reduced to little more than packaged DNA, while the other, the egg, retains its mitochondria and so provides the essential nurturing environment required for development. Hence the essential biological asymmetry between male and female in reproduction. Unlike our nuclear DNA therefore, our mitochondria are exclusively (Lane says almost) female in descent, a fact that has been used to study human ancestry from some so-called "mitochondrial Eve" living in Africa about 170,000 years ago - a story of which he is a little cautious.

      Like one of those elaborate word games in Round Britain Quiz, we now have the power and sex of Lane's title. As for suicide, this refers to the fact that, during development from the single fertilised egg to the fully formed adult, whether the few thousands of a tiny worm or the hundred trillion in the human body, many times more cells are born than survive; this over-production is, it seems, a necessary part of development and many of the cells that die en route are indeed "programmed" so to do, and it is their mitochondria, he argues, that generate the chemicals which kill them.

      Lane goes further; mitochondria, he argues, carry the secret of ageing and even potentially of postponing death. Whether this constitutes the meaning of life remains debatable. His book does not make for an easy read; it is eccentrically organised and packed with more detail than any other than committed mitochondriacs might wish to know. But embedded within it is one of the most interesting stories modern biology has to tell.

      · A new edition of Steven Rose's Lifelines: Biology, Freedom, Determinism, is published by Cape later this year. To order Power, Sex, Suicide for £17.99 with free UK p&p call Guardian book service on 0870 836 0875.

      Source: http://www.guardian.co.uk/books/2005/nov/12/featuresreviews.guardianreview10


      Power, sex, suicide Mitochondria and the meaning of life
      Reviewed by Eric A. Schon
      Columbia University, New York, New York, USA. E-mail: eas3@...
      Nick Lane
      Power, sex, suicide Mitochondria and the meaning of life.
      2005. Oxford University Press.: New York, New York, USA. 368p. ISBN: 0-192-80481-2 (hardcover).$30.00
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      To the typical reader of the JCI, the word mitochondria likely evokes a Pavlovian response remembered vaguely from biochemistry class: they are "the powerhouses of the cell." However, as implied by the title of this most thought-provoking book, Nick Lane goes to great lengths to remind us that they are much more than that.
      In seven broad sections, Lane takes us on a three-billion-year tour of the organelle, starting with the evolutionary origins of mitochondria, proceeding to their role in oxidative energy metabolism as well as their necessity for the development of complex multicellular organisms and - more provocatively - of sex, and ending with the recent discovery of their role in apoptosis and its implication for aging.
      Lane clearly loves this organelle, but unlike people who study mitochondria for a living, he has few axes to grind. This is not to say that Lane has no opinions (quite the contrary, the book is full of them), but those he has do not seem to be based on any particular bias a priori. Rather, Lane sets forth what we currently know about mitochondria - and his knowledge of the field is truly impressive, as he surveys major trends in evolutionary biology, cell biology, population biology and genetics, bioenergetics, power-law theory, and complexity, to name but a few of the fields covered - and then follows the data to likely logical conclusions. Where data are not available, he speculates freely, but also within the bounds of reason. Almost every area of mitochondrial biology is contentious, and it would be easy to be put off by Lane's self-assurance and his often purple prose, but, strange to say, I was not, even though I took exception to some of his conclusions.
      Of the seven sections in the book, I found the first and the last to be the most fun to read, as Lane provides his own spin on where mitochondria came from and where they are taking us. The prokaryotic origin of "endosymbiotic" mitochondria is now beyond debate, but how it happened has been contentious. Lane champions the "hydrogen hypothesis," in which a mutual relationship developed between two prokaryotes (one excreting H2 and CO2, and the other consuming them) that merged to ultimately become the ancestral eukaryote, a pairing so unlikely that Lane believes it happened only once on planet Earth and that its rarity may make multicellular life practically impossible elsewhere in the universe. I have enough arrogance to agree with the former, but enough humility to reject the latter.
      The chapters on apoptosis and aging that close the book are not only similarly thought-provoking, they should be required reading for workers in the field. Lane is particularly skeptical of the much-ballyhooed "free radical theory" of aging and makes the cogent point that free radicals not only need not be harmful, but may be absolutely beneficial. His discussion of aging in short-lived rodents as compared to long-lived birds, with its emphasis on the rate of free radical leakage through the respiratory chain, the detection of those free radicals, and the relative amount of "spare capacity" (that is, excess mitochondria) required for peak loads (for example, while flying), puts the aging problem into a perspective rarely seen in print.
      I found the chapters on sex and maternal (more properly, uniparental) inheritance the least persuasive. Lane argues that the "primordial" mitochondrial apoptotic machinery was the engine driving the origin of sex: in a damaged cell, selfish mitochondria could preserve themselves by encouraging the cell to fuse with an undamaged cell, thereby providing the mitochondria with a new cytoplasm with a more favorable redox environment, while at the same time recombination among the two nuclear genomes could repair the genetic causes of the initial damage. To limit the promiscuity of such an arrangement, this type of cell fusion was sequestered in the gametes and became the origin of sex. While Lane acknowledges the advantages of recombination to mask deleterious nuclear alleles, such an advantage would seem sufficiently powerful to evolve even in the absence of a mitochondrial raison d'etre. Moreover, rather than being a solution to the problem of "conflict" between male and female mitochondrial DNAs, uniparental inheritance can be viewed more simply as a way to prevent the spread throughout a population of deleterious mutations that manifest a phenotype only when present above a relatively high threshold of mutant mtDNAs, so that an isolated maternal lineage, but not the population, is eliminated once that threshold is exceeded.
      Lane is not particularly interested in the nuts and bolts of what mitochondria do; rather, he delves into the bigger questions of how mitochondria arose and why we eukaryotes, as "composite" organisms with the dual genetic heritages of mitochondrial and nuclear DNA, have come to be what we are. Surely that is a story worth telling. In Lane's hands, it is also one well worth reading. Ignore the ugly cover and buy the book.

      Articles from The Journal of Clinical Investigation are provided here courtesy of
      American Society for Clinical Investigation

      Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483179/

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