A recent study reported on a new way by which telomerase mediates its role in genomic stability. Essentially, it was found that telomerase has a mitochondrial targeting sequence [MTS (a way by which the cell can direct proteins to mitochondria)] and that its function in mitochondria was to make them more sensitive to oxidising molecules by inducing apoptosis. In fact, when the MTS in telomerase was experimentally disabled so that telomerase was prevented from entering mitochondria, cells were observed to be increasingly resistant to oxidant mediated apoptosis.
Initially, this function may seem paradoxical, yet it makes sense in cells with unlimited mitotic potential (able to divide indefinitely). In these cells, which include germ line and stem cells, a genomic mutation caused by oxidants from a malfunctioning mitochondrion could be propagated for the lifespan of the organism and potentially indefinately in the germ line. Therefore coupling the enxyme responsible for unlimited dividing potential - telomerase - to an increased level of quality control is a sensible evolutionary function.
If telomerase cannot enter mitochondria to perform its strict quality control, however, we potentially have a cell that whilst able to divide forever can also rapidly accrue mitochondrially generated mutagenic oxidants. Interestingly, a "switch" was discovered that regulated the ability of telomerase to leave its nuclear home so that it can localize to mitochondria and provide its quality control function. It would follow that if one could decrease oxidant concentration that less telomerase would be directed to mitochondria and another study reported precisely that.
Therefore, it may well be time to rethink the notion that telomerase is directly coupled to cancer and instead examine the role of proteins and mechanisms associated with facillitating the transport of telomerase into mitochondria.
The implications for WILT/SENS, for the treatment of cancer and for placing telomerase back on the longevity map are considerable.
