Re: mitochondrial DNA

Dear Jeff,

Mitochondria are fascinating organelles about which a great deal is known 
and a great deal is still to be learned. I’ll limit my answer to mammalian 
inheritance, since nature provides many variations in animals and plants on 
the theme of gender and fertilization, including hermaphroditic species, 
variable inheritance by different sexes, enormous variations in the size of 
mitochondrial genomes in different species, etc. You are correct in saying 
that mitochondrial DNA is inherited maternally in mammals. I’m not certain 
I understand from your question what the exact controversy is, but if you 
mean that sometimes, sperm mitochondrial DNA can be inherited by an embryo, 
I didn’t find any reports of that in my computer search of the MEDLINE 
database. Of course, the DNA in mitochondria in all the cells of males and 
females is subject to mutation by all the environmental factors and just 
plain mistakes during replication that affect nuclear DNA - cosmic rays, UV 
light, chemical damage, and so on. 

At the end of this message I have pasted two references, including the 
summaries, from the recent scientific literature that discuss maternal 
inheritance of mitochondrial DNA - one experimental, one theoretical. 
There’s a lot of cell biology terminology, but I think the gist of them 
will be helpful. 

In the first, there is a description of the fate of sperm mitochondria and 
re-organization of the cytoskeleton (protein filament systems) and other 
cell constituents observed under the microscope during in vitro 
fertilization in cattle. The sperm mitochondria appear to be partitioned in 
a defined way during the fist several cell divisions and then disappear, 
just as one might expect from what we know about the inheritance patterns. 
This constitutes visual confirmation of maternal inheritance.

In the second, there is an interesting hypothesis presented which says that 
the energy required for a motile gamete (i.e., the swimming sperm) depends 
on a very high rate of oxidative phosphorylation, which puts at risk the 
male mitochondrial DNA. The free-radical chemical by-procucts of this burst 
of energy production can cause mutations, and the author proposes that the 
division of labor and inheritance between the gametes from male and female 
is evolutionarily favored to provide the fertilized embryo with the 
highest-fidelity mitochondrial DNA. This provides a theoretical basis for 
maternal inheritance.

There’s another very hot area of research concerning mitochondrial DNA and 
mutations to it that is currently underway in many laboratories, one that 
your students may find interesting. Some scientists have been examining the 
hypothesis that aging in an individual is due in large part to an 
accumulation of mutations in mitochondrial DNA that build up over a 
lifetime in the various cells and tissues of our bodies. As mutations occur 
and slip past the repair mechanisms, energy production decreases, and 
slowly cells lose their ability to carry out their normal functions. This 
is a very attractive idea, and so far it appears to be consistent with the 
data obtained from tissue samples. 

I hope this answers your question. If not, please feel free to get in 
touch.

Paul Odgren, Ph.D.
Dept. of Cell Biology
University of Massachusetts Medical School
Worcester, MA 01655

The two references follow:

Biol Reprod 1996 Dec;55(6):1195-1205 

Fate of the sperm mitochondria, and the incorporation, conversion,
and disassembly of the sperm tail structures during bovine
fertilization.

Sutovsky P, Navara CS, Schatten G

Department of Zoology, University of Wisconsin, Madison 53706, USA. 

Sperm incorporation and the conversion of the sperm-derived components into 
zygotic structures during in vitro fertilization of bovine oocytes was 
explored by combining ultrastructural studies with observations of the 
fertilizing sperm tagged with a mitochondrion-specific vital dye 
MitoTracker green FM. The zygotes fertilized by the MitoTracker-labeled 
sperm were fixed at various times after fertilization and then processed 
for immunocytochemistry to examine the distribution of DNA, microtubules, 
and sperm tail components, including the fibrous sheath and axonemal 
microtubules. We show here that the complete incorporation of the sperm, 
but not sperm-oocyte binding and oocyte activation, depends upon the 
integrity of oocyte microfilaments and is inhibited by the microfilament 
disrupter cytochalasin B. After sperm incorporation, the mitochondria are 
displaced from the sperm's connecting piece, and the sperm centriole is 
exposed to the egg cytoplasm. This event is followed by the formation of 
the microtubule-based sperm aster, which is responsible for the union of 
male and female pronuclei. Concomitantly, the major structure of the sperm 
principal piece, the fibrous sheath, disappears. After the first mitosis, 
the compact mitochondrial sheath can be seen in one of the blastomeres. An 
aggregate of the sperm mitochondria is observed at the entry of the second 
mitosis, although they remain in the vicinity of the nucleus and can later 
be seen at one pole of the metaphase spindle. The mitochondrial cluster is 
occasionally found in one of the blastomeres in the early-stage four-cell 
embryos, but it is no longer detected by the beginning of the third mitotic 
cycle. These data suggest that the disassembly of the sperm tail during 
bovine fertilization occurs as a series of precisely orchestrated events 
involving the destruction (fibrous sheath and mitochondrial sheath) and 
transformation (DNA, sperm centriole) of particular sperm structures into 
zygotic and embryonic components. 

J Theor Biol 1996 May 21;180(2):135-140 

Separate sexes and the mitochondrial theory of ageing.

Allen JF

Department of Plant Cell Biology, Lund University, Sweden. 

An hypothesis is presented by which gamete specialization resolves a 
conflict between the function and replication of mitochondria. The function 
of mitochondria is to synthesize ATP by oxidative phosphorylation, which is 
coupled to respiratory electron transport. This requires a mitochondrial 
genetic system. However, "incorrect" electron transfers produce free 
radicals that cause mutation, and the frequency of these events is 
increased by mutation. Mitochondrial function is therefore detrimental to 
the fidelity of mitochondrial replication. Damage to somatic mitochondrial 
DNA may accumulate within, and indeed determine, the life span of 
individual organisms. Motility of one gamete is required for fertilization, 
and requires ATP. It is proposed that male gametes maximize energy 
production for motility by sacrificing mitochondrial DNA to electron 
transfer and its mutagenic by-products, while female gametes, whichare 
non-motile, repress mitochondrial oxidative phosphorylation, thus 
protecting mitochondrial DNA for faithful transmission between generations. 
Male gametes then make no contribution to the mitochondrial genome of the 
zygote: mitochondria are maternally inherited. This testable hypothesis may 
help to explain the evolution of separate sexes and a number of their 
characteristics. Maternal inheritance of chloroplasts may be explained in a 
similar way, and contribute to the maintenance of separate sexes in plants.