The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

The Search for How Mutant mtDNA is Amplified
Fig. 8.2. Mutant mtDNA preferentially evades destruction.
8.2). Furthermore, it shares with SOS the additional advantage of providing an explanation
for why mitochondrial turnover happens at all. I present it here, rather than with the other
preferential replication-based models (see Sections 8.1 and 8.2), partly because I was unaware
of it at the time I formulated SOS: it was proposed 6 only negatively, as a circumstantially
unlikely alternative to the cis-regulation model. It must still be considered a candidate for
the actual mechanism of clonal amplification of mutant mtDNA: there is some experimental
evidence against it, but not enough (in my view) to rule it out quite yet.
The essence of this idea is that the individual mitochondrion, not the cell, is the entity
that controls the timing of its replication. There is proposed to be a pool of raw materials for
mitochondrial replication available in the cytosol, which a mitochondrion imports when
triggered to do so by some aspect of the intramitochondrial environment—most simply,
shortage of matrix ATP. Shortage of ATP can be caused by self-inflicted proton leak, so
mitochondrial replication in non-dividing cells will result. The role of lysosomal degradation
is then at the tail of the causal chain, as the random destruction of mitochondria (irrespective
of their integrity) when the cell simply has too many. In rapidly-dividing tissue, a mechanism
for homeostasis is also available: cell division requires cell growth, which dilutes cytosolic
ATP; intramitochondrial ATP is thus exported more rapidly, so intramitochondrial ATP
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