questions about mitochondria

Iuval Clejan clejan at mindspring.com
Fri Aug 11 20:21:05 EST 2000


Jim Cummins wrote:

> In article <3990E304.5B9BBD51 at mindspring.com>, Iuval Clejan
> <clejan at mindspring.com> wrote:
>
> > I hope some kind soul answers these questions from a physicist who is
> > pretty ignorant of biology (not just Aubrey):
> >
> > 1. Can there be a mechanism of segregation of "bad" mitochondria into 3
> > of the four oocytes that form from one oogonium, and good mitochondria
> > into the viable oocyte?
> Only one of the daughters forms the ovum - the rest are the polar bodies
> destined to be discarded. You can certainly amplify mtDNA from the polar
> bodies and this has been propsed as a diagnostic tool for mtDNA disorders
> in early embryos (Briggs et al. Amplification of DNA sequences in polar
> bodies from human oocytes for diagnosis of mitochondrial disease. Lancet
> 2000; 355: 1520-1521.). I know of no evidence of differential segregation.

I assume you mean amplify by PCR. Has anybody tried to amplify defective DNA
from polar bodies vs from the ovum and compare? In other words, is the lack of
evidence due to the fact that nobody has looked for evidence?

>
> >
> > 2. Actually I don't understand oogenesis. My understanding is that
> > mitosis occurs a few times in the embryo and that the cells are then
> > called oogonia. After the first meiotic division the cells are called
> > primary oocytes (diploid?). And after the second meiotic division (which
> > occurs during sexual maturity) the cells are called secondary oocytes.
> > Is this correct? Some people have told me that meiosis is not complete
> > until ovulation (how so?)
>
> The primary oocytes enter a dictyate resting stage during fetal life (I'm
> talking mammals here).  Meiosis only resumes around ovulation and in fact
> activation of the oocyte (normally by sperm penetration) is the trigger
> for the second meiotic division.

Huh? So when does the first meiotic division occur?And what are the secondary
oocytes? I thought that when the sperm penetrates the egg you start dividing
by mitosis again. Isn't the egg before fertilization haploid (as is the
sperm)? In which case it has already undergone the second meiotic division.
Please explain. What about the drosophila question?

>
> >
> > 3. What proteins that are involved in mitochondrial welfare are coded
> > for by the nucleus? Anything for repair of mtDNA? Replication of mtDNA/
> > transcription of mtDNA? Why is tellomerase anti-apopototic? Is it
> > possible that senescent cells stop expressing some of the genes
> > necessary for mitochondrial welfare? I am thinking that one of the main
> > differences between mitos and aerobic bacteria is that mitos are
> > symbiotic with the nucleus, whereas bacteria are rugged individualists.
> > So what if mitos are mutating at a high rate, so are bacteria, as long
> > as they keep reproducing they will survive. One thing that might keep
> > them from reproducing is a nuclear clock (e.g. tellomere shortening
> > followed by activation of P53 followed by apoptotic signals) This
> > scenario would favor mitos in post mitotic cells, if other mechanisms
> > didn't come into play.
>
> In mammals the vast majority of maintenance genes have translocated to the
> nuclear genome and the only ones left appear to be the minimal set
> required for OXPHOS. It's certainly possible that senescence involves
> decay in these.

I was hypothesizing that senescence involves decay in the nDNA or some
activation of a pathway triggered by telomere shortening, NOT by the mtDNA.

> In sharp contrast to the over fifty pathogenic mutations
> described in mtDNA, only one disease-causing mutation has been identified
> in a nuclear gene, that encoding the flavoprotein subunit of complex II
> (Bourgeron et al., 1995). This situation will certainly change in the
> years to come because there is good, if indirect, evidence that many
> generalized syndromes are due to mutations of nDNA-encoded subunits of the
> respiratory chain (Di Mauro et al., 1998)
>
> --
> Jim Cummins
> Murdoch University
> <cummins at central.murdoch.edu.au>







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