RE: specific amino acid restriction does the same thing as calorie restriction?

From: Rafal Smigrodzki (rafal@smigrodzki.org)
Date: Tue Apr 22 2003 - 10:40:41 MDT

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    Damien wrote:
    > calorie restriction?
    >
    >
    > At 04:17 PM 4/21/03 -0700, Rafal wrote:
    >
    >> I like your idea of transferring
    >> mtDNA-encoded function to the nucleus. Any more information on this
    >> project?
    >
    > I like the idea of using heavy-duty nuclear maintenance and repair
    > mechanisms to keep our mitos nice, but I find it hard to see how this
    > would work. You surely can't replace the work of a zillion
    > cytoplasmic machines by one or a hundred nuclear-embedded versions.
    > Besides, wouldn't that require the helix to be pulled open and naked
    > all the time at that locus, which can't be a good look for DNA.
    >
    ### Aubrey would be more competent to answer these objections but let me try
    too:

    Most of the proteins in mitos are nuclear-encoded anyway. The way the
    nuclear genes, usually present in only two copies, achieve large protein
    output is by having relatively stable mRNA's which act as amplifiers of
    their function. If you transfer the mtDNA to the nucleus and set the
    nuclear-encoded mtRNA polycistronic transcript to a high copy number (by
    stabilizing it in the cytoplasm), you should be able to make the same amount
    of protein as made from the 10,000 mtDNAs currently present in our cells.

    I don't know if there is an increase in the mutation rate at highly
    transcriptionally active loci (where the sense DNA strand indeed has to be
    pulled open for the RNA to be synthesized), but this couldn't be a higher
    mutation rate than what you have in the mtDNA now, with all mitos actually
    recycling their DNA about every two weeks, as compared to once ~70 years for
    some neurons. Also, transcription in the nucleus, behind the nuclear
    membranes, might be safer than being in the mitochondrion, with all the free
    radicals generated in close vicinity. Something like keeping the chips
    encoding a nuclear plant's safety measures in the manager's office as
    opposed to the reactor enclosure.

    Rafal

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