RL: We know that mitochondria may indeed be endosymbiotes in the sense
that millions of years ago, these tiny bacteria were engulfed by larger cells
and ultimately evolved to be co-dependent with our cells.
We provide them with foodstuffs and protection from predation,
and in turn, they provide us with the majority of the ATP energy currency
that our cells need to do work.
What you may not realize, however, is that each mitochondrion
has its own DNA, its own genome.
So what that means is that while we are accustomed to thinking of our cells
and their genomes in terms of what exists in the nucleus,
all of the genes that we think of as the ones we inherit from our mother
and from our father, we cannot forget that the mitochondria in every single
cell also carry their own DNA genomes.
Now, where did those DNA genomes come from?
Well, another interesting fact is that we only
get mitochondria from our mothers.
The mitochondria come with the egg, while the sperm
that we got from our fathers, in terms of fertilization,
do not contribute any mitochondria to what
will ultimately develop in embryogenesis into us, into an adult human being.
So this is, of course, a debt that we owe are mothers.
They are the source of our mitochondria.
But then if you want to think about what we inherit and are there
possible mutations that we might inherit,
we can't just think about what we inherit
in terms of the nuclear genomes-- what we inherit from our father
and from our mother-- we also must think about what mitochondria we inherited
from our mothers.
It was fairly recently when we discovered
that there are a number of human diseases--
usually metabolic diseases-- that are tied to the inheritance of mutations
in the mitochondrial genome.
Many of these diseases, as you might expect,
are related to lower than normal levels of ATP or defects, for example,
in the electron transport chain.
Defects that really affect, if you will, the energy
metabolism that we all need so crucially for all of life's processes.
So the question is, where did these defects come from in mitochondria,
and how can we understand the process of inheritance that occurs?
Let's begin by thinking about a cell's mitochondria
and what the makeup of those mitochondria might look like.
So if we have a cell from our bodies, we have a nucleus,
and then we may have multiple mitochondria in a cell.
Usually we'll have anywhere from 10 to 20 mitochondria.
Now, when we think about this, we generally
think of the nuclei or a single nucleus in a single cell
as having a particular genome.
But what we don't usually think about is that the mitochondria in a cell
are in fact a population.
They are not all the same.
And in particular, if you think about their genomes,
their genomes may not be all the same.
So here we're shown a number of mitochondria,
and we're distinguishing their genomes by color.
So we have, let's say, four mitochondria that we're
designating as having one particular genome in purple.
We have two in pink, and we have three in orange.
Now let's suppose that there's a defect in the mitochondrial genomes,
and the defect is associated with these two mitochondria that are pink.
What this means is that the defects are associated with two mitochondria,
but we have another four, in fact, seven mitochondria that
are otherwise perfectly healthy.
And so when it comes to the state of that cell,
whether or not there's a negative impact of those mutations
will depend on how many mitochondria are defective.
Mitochondrial diseases are really quite devastating.
If you think about it, it's not really surprising,
because given the role that mitochondria play in providing the majority of ATP
that we need, any disease that disrupts their ability
to produce ATP, to manufacture ATP can have significant metabolic impacts.
So mitochondrial disease often involves, for example, muscle weakness
and wasting, because muscles use a significant amount of ATP.
It also can involve cognitive defects, sort of degeneration of the brain,
because as one would expect, neurons or nerve cells in the brain
also utilize an enormous amount of ATP.
How common are mitochondrial diseases?
They're really one of the more common kinds of genetic diseases.
For example, in the United States, where you'll see a frequency of roughly 1
in 5,000 to 10,000 births might have some kind of mitochondrial disease.
Because of the severity or the possible severity of mitochondrial disease,
you also frequently see lethality by age two.
So that quite often if there's a severe expression of a mitochondrial disease,
you might have a stillborn kind of situation,
or you may also have a case where the child dies by age two.
So clearly, this is a very severe kind of disease,
but it also reveals a remarkably different kind of inheritance
than anything we've seen before.
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