Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sun Jul 29 11:52:43 EST 2001

Iuval Clejan wrote:

> I don't know if my previous message went through. Seems like it didn't
> (but I don't know for sure since I'm posting through google) so I'll
> try again.

Your previous message and my reply are visible at


> I want to know if Mn-Cu SOD can be transported in  small
> but significant quantities into mitochondria, and once there if it can
> be catalytically active and protect the membrane from ROS.

To summarise my previous reply: not into the mitochondrial matrix (the
space enclosed by the inner membrane), but maybe into the intermembrane
space, where it could indeed be protective.  And it's CuZn, not MnCu.

> I'm interested in the etiology of higher ploidy in liver cells and one
> article found that this was weakly inhibited when mice had extra Mn-Cu
> genes. Is it possible that the Mn-Cu SOD protected mitochondria? Or is
> this more likely a cytosolic effect?

I presume you're referring to Nakatani et al, Exp Cell Res 236:137-146.
(Please get into the habit of including citations when you reference
published work in postings.)  This SOD is highly unlikely to have got
into the intermembrane space, because it has no targeting sequence.
(That's not an absolute proof, because the intermembrane space protein
cytochrome c also has no known targeting sequence, but it's strong
evidence.)  There is a mention of something that the article calls
"mitochondrial CuZnSOD", but it references a paper (Tsai et al, Biochem
Int 28:205-217) that I haven't seen, so I wouldn't like to speculate on
what was actually measured.  I have no more idea than Nakatani et al
what regulates hepatocyte ploidy, nor whether it is particularly bad
for us.

I actually don't see what you're getting at with regard to the role of
mitochondrial damage (or protection from damage) in this.  Just to make
sure you understand: the ploidy being discussed is of the nuclear genome,
not the mtDNA.

Aubrey de Grey

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