Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Jul 28 14:54:41 EST 2001

Iuval Clejan wrote:

> Thanks, Aubrey. These enzymes are probably found in some concentration
> in all three places though, it is probably not a binary thing. Do you
> have any idea how much Mn-Cu SOD there is in mitochondria of
> hepatocytes (even though most of it is cytosolic and extra-cellular)?
> Also, even if some Mn-Cu SOD exists in mitos, can it be catalytically
> active at mitochondrial Ph?

1) Pay attention -- there is MnSOD and CuZnSOD; there is no such thing
as Mn-Cu SOD.  Also it is pH, not Ph.  Details matter in science....

2) Nuclear-coded proteins don't get into mitochondria by accident, only
by virtue of possessing signals that get them bound to the mitochondrial
protein import machinery.  Conversely, the metal atom of MnSOD is only
introduced after import (since import entails complete unfolding), so
MnSOD is not catalytically active in the cytosol.  So this is as close
to a binary thing as you will find in biology.

3) However (and maybe this is where your question originates), there is
a school of thought that an isoform of CuZnSOD may be present within the
mitochondrial intermembrane space (in contrast to MnSOD, which is in the
matrix).  Opinion on this has oscillated wildly over the years; first it
was there (1), then it was not (2,3,4), then early last year it was (5),
then the paper arising from that last study was withdrawn, now there are
rumours that others have found it....  Watch this space.  For sure it is
going to be some time before we can say anything about concentrations,
even if they turn out to be non-zero.

Aubrey de Grey

1) Weisiger and Fridovich J Biol Chem 1973; 248:4793-4796
2) Geller and Winge, J Biol Chem 1982; 257:8945-8952
3) Liou et al.,  Free Radic Biol Med 1993; 14:201-207
4) Balzan et al., Biochem Biophys Res Commun 1999; 256:63-67
5) Fridovich I. Mitochondrial Cu,Zn superoxide dismutase revisited. In:
   International Congress on Oxidants and Antioxidants in Biology, Book of
   Abstracts, 2000, p. 82

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