Introducing Mitome. Determine your "mitochondrial type" with my first-in-kind direct-to-consumer respiratory chain test that generates a personalized protocol.

Installment 2:.

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I hereby dub melatonin the “guardian angel” of the mitochondria because:

. and leaves the mitochondria to act on the outside of the mitochondrial membrane in a way that fundamentally protects the mitochondria from stress, and that this protective effect goes far beyond the stress imposed by circadian disruption.

However, we will see in the next installment of this series that melatonin is synthesized in the mitochondria, consumed in the mitochondria. .

You can see in the above figures that melatonin is very enriched in brain mitochondria, and just moderately higher than the nucleus and cytosol in liver.

So it is likely that the energetic stress of circadian disruption is fundamentally a matter of failing to adequately prepare for the energetic shifts that are supposed to occur as we transition between sleeping and waking.

This requires adequate preparation for a number of reasons:

Data from rodents, non-human primates, and humans collectively suggest that there is a natural rhythmic ebb an flow of oxygen consumption that makes the mitochondrial respiratory chain slow down across the duration of the sleeping period and perk up when we are active.

Their daily rhythms of cortisol, insulin sensitivity, movement, and food intake become completely destroyed.

Even though bright light at night puts these rodents to sleep instead of keeping them up, it still disrupts their circadian rhythm and causes them to become obese and diabetic.

Rats an mice are nocturnal, yet their plasma and pineal melatonin behaves the same as that of humans’ in response to light.

The authors thought this was from melatonin deficiency, but they didn’t measure the cellular melatonin. We know from the study above that it goes up. So circadian disruption puts stress on cells, they respond by increasing melatonin synthesis, but they don’t synthesize enough.

Removing the pineal gland from rats causes oxidative stress, oxidative damage, and inflammation in their eyes that is reversed by supplementing them with 5 milligrams per kilogram bodyweight melatonin.

Well, the fact that intracellular melatonin synthesis flips into high gear during the stress of circadian disruption gives us a clue.

In watch of what?.

My suspicion is the rapid disappearance of melatonin from plasma has almost nothing to do with its catabolism and almost everything to do with its cellular uptake. Inside cells, melatonin is not rapidly degraded. It largely sits there in watch.

Second, if you look at the diurnal variation, while there is no clear spike during the darkness, you can make out a general trend for melatonin to slip upwards during the dark and downwards during the light.

First, because, unlike serotonin, melatonin is fat-soluble enough to easily slip across cell membranes in a completely unregulated fashion. That is also why the melatonin seems to disproportionately accumulate in the membranes in this study.

Why?.