The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

CHAPTER 2
An Introduction to Mitochondria
Mitochondria have two main characteristics which, in combination, mark them out among
subcellular structures as especially plausible mediators of cellular decline. The first is
their absolute indispensability to the cell: they are the intracellular machines that enable us
to use oxygen, and they are also intimately involved in other aspects of cellular stability. The
second is their vulnerability: they constantly inflict damage on themselves as a side-effect of
aerobic respiration, and they have one small but vital component which is not reconstructible
from scratch, so damage to which may be permanently harmful to the cell—their DNA.
Their structure and function are both highly complex and will be covered in detail in,
respectively, Sections 2.2 and 2.3; Section 2.4 focuses on the mitochondrial DNA (usually
abbreviated mtDNA) itself.
This description of mitochondria begins, however, with a summary of how they are
believed to have arisen during evolution. At first sight, this question may seem to be unrelated
to the subject of age-related mitochondrial dysfunction and its causes and effects. In fact,
however, one of the main fascinations of studying “how we got into this mess in the first
place” (as evolution has often been described) is the frequency with which an understanding
of it sheds light on matters of more immediate concern. The topics covered in this book are
no exception.
2.1. The Evolutionary Origins of Mitochondria
The macromolecular composition of mitochondria is almost entirely proteins and
lipids—the same basic components as the rest of the cell. The cell makes these on demand.
But the creation of a new mitochondrion also entails the creation of a new copy of that
small but absolutely vital piece of genetic material, the mtDNA. This—like the DNA in our
chromosomes—cannot be made from scratch, only by duplicating an existing copy. For
that reason above all, the way cells make a new mitochondrion is by replicating an existing
one to make two. (It is more accurate to say that “the cell replicates the mitochondrion” than
that “the mitochondrion divides,” because not one of the proteins that are involved in the
replication process is encoded in the mitochondrial DNA. All of them—for example, the
components of the enzyme that replicate the mtDNA, which is called DNA polymerase
gamma—are encoded in the nucleus.)
A logical conundrum clearly arises from the situation just described: if the only way to
make a mitochondrion is by starting with a pre-existing one, then where did the first one
come from? There are plenty of mitochondria in egg cells, so we have no problem transmitting
them from one generation to the next; but there must have been a first mitochondrion at
some time in our evolutionary history.
The fascinating answer, which is now universally agreed, was proposed in the
1920s 1 —indeed, arguably 40 years earlier 2,3 —but was almost universally rejected as
altogether too preposterous, even as recently as 1966, 4 until it was revived in 1967. 5,6 Recall,
The Mitochondrial Free Radical Theory of Aging, by Aubrey D.N.J. de Grey.
©1999 R.G. Landes Company.