mitochondria and apoptosis

Aubrey de Grey ag24 at mole.bio.cam.ac.uk
Sat Sep 12 07:21:57 EST 1998


spring wrote:

> I have recently come upon an article that claims that apoptosis is
> controlled by mitochondria. First is there enough evidence for this (I
> only read the abstract)?

"Controlled" is not the word I would use (not in most cases of mammalian
apoptosis, anyway), since the originating signal that triggers apoptosis
of a given cell usually comes from outside the cell, but yes, mitochondria
play a central and quite early role in apoptosis.  A small protein called
cytochrome c, which is normally part of the respiratory chain, was "to
general stupefaction" (I quote a recent paper) discovered, only a few
years ago, to be massively released from mitochondria into the cytosol
shortly before apoptosis occurs.  We now know that, when released, it
initiates a cascade of activation of special proteases called caspases,
which do much of the actual work of apoptosis.  All the above is now
established beyond doubt -- it is an extremely hot topic so there is a
lot of literature.  A recent review in Science 281(5381):1309-1312 (just
a couple of weeks ago) is a fine place to start if you want to know more;
there are several other reviews of aspects of apoptosis in the same issue.

> Second, Might this have any bearing on [organismal] senescence?

Only if apoptosis itself does, I would say, and the chances are that the
opposite is true -- that apoptosis positively retards organismal aging,
since it is a way for the body to eliminate damaged and potentially toxic
cells.  Turning this on its head one might conjecture that, for example,
mtDNA mutations might impede the mechanism of release of cytochrome c,
thereby not allowing apoptosis to proceed when desired and causing the
accumulation of toxic cells, but there is as yet no evidence (that I know
of) implicating any of the mt-coded proteins in the apoptotic mechanism.
(Cytochrome c itself is nuclear-coded.)

Aubrey de Grey




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