The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

6
The Mitochondrial Free Radical Theory of Aging
firstly, that cells of the type we are made of are not the only ones that exist. Organisms
(whether made of one or more cells) whose cell(s) have a nucleus are called eukaryotes.
Bacteria are not eukaryotes; they are called prokaryotes, and their structure is much simpler.
They do not have a nucleus; nor do they have mitochondria. Also, their DNA is not divided
into chromosomes, as ours is; instead it is all in one molecule. Furthermore, that molecule is
circular, whereas all eukaryotic chromosomes are linear. What intrigued Wallin, 1 and
subsequently Margulis (née Sagan), 5,6 is that mitochondria share all these (and other) features
of bacteria! (Except that Wallin didn’t know about the DNA, of course.) They don’t have a
nucleus; they don’t have their own mitochondria, and their DNA is a single circular molecule.
Additional, subtler similarities have been emerging ever since. For example, superoxide
dismutase (an enzyme with a pivotal role in MiFRA, which we will encounter often in this
book) exists both inside mitochondria and outside, but in very different forms; the metal
cofactor of the mitochondrial form is the same—manganese—as in a bacterial superoxide
dismutase, whereas the non-mitochondrial one uses copper and zinc.
So, it is now firmly believed that the sequence of events which created what we now
know as mitochondria was as follows (see Fig. 2.1). Early bacteria were unable to use oxygen,
and in fact it was highly toxic to them. Then aerobic respiration evolved in some bacteria.
Independently of this, other bacteria evolved a nucleus, linear chromosomes and the other
features that made them eukaryotic cells. Then a bacterium which was capable of aerobic
respiration was phagocytosed—engulfed, in plain English—by a single-celled eukaryote,
and by some outlandish quirk it was not immediately destroyed. It carried on living, inside
the eukaryotic cell. Furthermore, it was still able to divide, producing more bacteria, all still
inside this cell.* When the cell divided, some bacteria ended up in one daughter cell and
some in the other. The bacteria were extremely useful to the cells, because they sequestered
any toxic oxygen that was around and made energy out of it; thus, the cells with these bacteria
inside them were able to multiply faster than the ones without. (Likewise, the cells were
useful vehicles for the bacteria. This kind of mutually beneficial relationship between two
organisms is called symbiosis, and in this case where one of the participants is living inside
the other it is called endosymbiosis. Thus, this theory is called the endosymbiotic theory.)
Over time they outcompeted the cells that had no aerobic bacteria inside them, so that soon
almost all eukaryotic cells had not only nuclei but also bacteria performing aerobic
respiration. Since then, not much has changed.
The main thing that has changed concerns the DNA of the phagocytosed, aerobic
bacteria. It is that very nearly every gene in those original bacteria has either been lost from
the bacterial (now mitochondrial) DNA, due to redundancy with a gene already present in
the nucleus, or else has been transferred to the nuclear DNA. This is how, as noted above,
enzymes such as the mitochondrial DNA polymerase came to be encoded in the nucleus:
the genes didn’t evolve there, they moved. This is not a trivial event, because proteins encoded
in the nucleus are constructed outside the mitochondrion and have to be transported into it
to do their job, as will be discussed in Section 2.4.3 and elsewhere.
* Possibly the most implausible aspect of this engulfment—the "endosymbiotic event"—is that the bacterium
was able to cope with such a sudden change in its external environment, from being in the outside world to
being inside another cell. This aspect of the theory has more recently been improved by hypotheses that
propose a very gradual engulfment, starting out as a normal symbiosis of two species which used each other's
metabolic waste products—perhaps sulphur, 7 perhaps hydrogen 8 —as nutrients; slow changes in the geological
conditions then promoted an ever-closer union of the two which eventually became an engulfment.