As we sit inside our cozy homes, in front of the fireplace that brings us warmth and energy, we feel the benefits and all seems well. What happens if smoke from the fire started billowing out into the room? We are immediately alerted, smoke alarms go off, we are moved to immediate action. We realize that besides providing energy, fires can be dangerous. Fire produces smoke, free radicals, carbon monoxide, sparks and ash, fires can get out of control. In order to harness the ample benefits of fire, we have made special places in our homes where the fires can be controlled. We have devices that control the fire, harvest the energy, and alert us if the smoke builds up. This scenario provides us a great analogy of what is happening inside our trillions of cells. Inside every one of our cells, fuels are delivered, like oils and gasoline (fatty acids and sugars), that burn with the provided oxygen inside an average of 200 controlled furnaces (called mitochondria) in every cell, this fire produces smoke (ROS) that is eliminated by scrubbers (antioxidants) and detected by smoke detectors (thioredoxin semaphores, Nf-kappaB). All of these devices must be in place inside our cells to harness the energy of these metabolic fires.

At the junctions inside the cells where the oxygen pathways and fuel pathways merge, the fire of life provides energy. Even on a molecular level, nothing happens without energy. The major reason that we search for food and take in oxygen is to provide the fuel molecules and oxygen molecules maintain these vital fires of life inside our cells. Within this fire of life, the universal energy molecule, ATP, is forged. ATP powers all of the molecular machines, players, instruments, everything that requires energy in our cells. Every time you blink an eye, think a thought, twitch a muscle or feel a breeze, trillions of ATP molecules are spent to fuel the action. If the fire of life were to go out, in seconds the cell would run out of its supply of ATP energy molecules and the concert of life in the cell would quickly come to an end. There is nothing more important to a cell than to keep these fires burning.

The “smoke” that comes out of these cellular fires, reactive oxygen species (ROS), composed mostly of superoxide free radicals (O2*-) and hydrogen peroxide (H2O2), increases when the fires of life flare up inside the mitochondrial furnaces. These ROS (smoke) molecules affect the semaphore molecules (smoke detectors) that, in turn, change “color” and redirect molecules along the pathways. In other words, these smoke detectors are intelligent and are wired to make changes inside the cell. This is at the essence of redox signaling. The ROS superoxide free radicals (O2*-) and hydrogen peroxide molecules (H2O2), just like smoke, are highly energetic and reactive, and can also damage certain sensitive structures in the cell (like the DNA). Thus plant and animal cells have adapted to produce various types of antioxidant enzymes (smoke scrubbers), such as glutathione and SOD that can eliminate ROS “smoke” and keep it out of sensitive areas. As might be expected, these antioxidant enzymes are tightly regulated and controlled by redox signaling networks. For example, too much hydrogen peroxide in the cell will activate the redox signaling semaphores along pathways that turn down the metabolic fires and increase the production of antioxidants (smoke scrubbers) needed to eliminate the ROS (smoke).

Many of the redox regulatory processes are aimed at maintaining proper homeostatic balance of redox potentials in all the fluids in the various parts of the cells and tissues. Shifts in the redox potential (smoke signals) of vital fluids in and around the cells will generally activate redox signaling pathways that are designed to ultimately return the redox state to “normal” again. In the past decade, we have learned that it is dangerous to try to force the elimination of all superoxide free radicals or hydrogen peroxide in our body. In fact, the body will try to counterbalance any efforts to change the established natural balance by producing more of the lacking species to compensate. In order to maintain life processes, we require well-balanced control of these types ROS in our body. There are a variety of redox signaling pathways that naturally maintain normal redox balances and potentials throughout all the fluids in our body. Without both the oxidants and the antioxidants inside these vital fluids, this homeostatic balance would quickly be destroyed, and we would surely die. ROS is an essential signaling molecule.

If we were to completely eliminate the smoke from the fires inside our cells, the smoke detector semaphores would not be activated when the fires flare up and get out of control. ROS smoke is required to make the whole system work. Without ROS smoke, the damage detection mechanisms are shut down. In the vast majority of cancer cells, for example, the redox signaling system has been shut down, the mitochondrial furnaces have been shut down, the redox detection semaphores (smoke detectors) are not able to work. Without the aid of this redox signaling system, these damaged cells cannot be effectively detected, repaired or destroyed; they become immortal and remain broken. Smoldering fires are not extinguished, damage is propagated. Life is threatened.

As we contemplate these concepts, we realize that life is preserved by those devices inside our cells that maintain proper redox balance. It creates that cozy space inside our cells, where all is well; the fires are burning at their proper level, the smoke is being handled and the energy efficiently harnessed. When fires flare up, smoke billows out, alarms go off, smoke detectors are activated that will push the genes that will bring it all back into control. That is one description of redox signaling.