Study in a cell showing that runaway mitochondria cause telomere damage in cells; the first concrete evidence for the long-held belief that sick mitochondria pollute the cells they are supposing to be supplying with power. This involving a causal experiment to kick off a mitochondrial chain reaction that wreaks havoc on the cell, all the way down to the genetic level.
At this point, the nucleus of the cell is being pummeled by free radicals. It shrinks and contorts. The cell stops dividing. Yet, the DNA seems oddly intact. That is, until the researchers start looking specifically at the telomeres the protective caps on the end of each chromosome that allow them to continue replicating and replenishing.
Telomeres are extremely small, so DNA damage restricted to telomeres alone may not show up in a whole-genome test, like the one the researchers had been using up to this point. So, to see the genetic effects of the mitochondrial meltdown, the researchers had to light up those tiny endcaps with fluorescent tags, and lo and behold; they found clear signs of telomeres fragility and breakage.
Mitochondria cause telomere
Then, in a critical step, the researchers repeated the whole experiment on cells with inactivated mitochondria. Without the mitochondria to perpetuate the reaction, there was no buildup of free radicals inside the cell and no telomere damage. Basically, we shut the machine off before it had a chance to do any damage.
But these findings could be using for improving photodynamic cancer therapy; which involving bombarding solid tumors with reactive oxygen species using light delivering with fiber optic cables. One thing his team discovering in the course of these experiments is that inhibiting ATM a protein; that signals DNA damage magnified the damaging effects of the reactive oxygen species spewed out by the mitochondria. The cells not only shriveling.
Combining photodynamic therapy
By combining photodynamic therapy with ATM inhibition; it may be possible to design a system that effectively kills cancer cells with light. But the events involving mitochondrial dysfunction and subsequent nuclear oxidative stress that resulted in specific telomere damage; we delineated the mechanism of mitochondria telomere axis of cellular damage.
But it is highly controversial whether secondary reactive oxygen species generating by dysfunctional mitochondria are able to diffuse across the cytoplasm to the nucleus; and cause subsequent nuclear changes. Our findings revealed a fundamental mechanism underlying the pathophysiological role of mitochondrial singlet oxygen; with important ramifications for understanding the role of mitochondrial signaling in aging and cancer among other human diseases.