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February 4 - April 8, 2025
Mitochondria are tiny. On average, each human cell has about three to four hundred mitochondria.3 This means that there are about ten million billion mitochondria in the human body. They make up about 10 percent of our body weight despite their tiny size.
Mitochondria are busy. Although small amounts of ATP can be produced without mitochondria through a process called glycolysis, mitochondria produce the lion’s share of ATP, especially for brain cells.
a single neuron in the human brain uses about 4.7 billion ATP molecules every second.5 That’s a lot of ATP!
Why are they moving? Well, one reason is that they appear to go to the places in the cell where things are happening and where energy is needed. Energy needs to be produced in the right amount, in the right place, at the right time, and it goes through an unimaginably fast recycling process that involves mitochondria. The mitochondria that aren’t moving appear to stay in places where things are always happening—either near factories where proteins are made (ribosomes) or synapses where there is a lot of activity, which is a very important fact relevant to how the brain functions.
Mitochondria are rapid recyclers.
This ADP can’t supply much energy anymore, but if a phosphate group is added back to it, it’s as good as new. That’s what mitochondria do. They take ADP and turn it back into ATP by attaching a phosphate group, then transfer it out to the cell cytoplasm where it is needed.
You can think about mitochondria as little vacuum cleaners, going around the cell and sucking up ADP and churning out ATP.
all the symptoms of mental illness are directly related to mitochondria and metabolism.
High levels of calcium in the cytoplasm can trigger all sorts of things to happen. In many ways, calcium is an “on/off” switch.
mitochondria are essential in turning cells both on and off. They provide the energy needed for ion pumping, and they also regulate the calcium levels that function as essential on/off signals.
a peptide called humanin was first reported to have broad effects on metabolism and health.
MOTS-c and SHLP1–6, have been discovered and added to a new class of molecules called mitochondrially derived peptides.
mitochondria are able to communicate with each other through these peptide signals in order to regulate metabolism throughout the body.
Neurotransmitters have been a primary focus in the mental health field. It turns out that mitochondria play critical roles in their production, secretion, and overall regulation.
Mitochondria provide both. They play a direct role in the production of acetylcholine, glutamate, norepinephrine, dopamine, GABA, and serotonin.
Vesicles filled with neurotransmitters travel down the axon to get to their ultimate release site. That takes energy.
Once that signal comes, the actual release of neurotransmitters also takes energy.
After they are released from the receptors on the target cell, they are sucked back into the axon terminals (a process called reuptake), and you guessed it, that takes energy. They are then repackaged back into vesicles for the next round—yet more energy.
When mitochondria aren’t functioning properly, neurotransmitters can become imbalanced.
The role of mitochondria in regulating neurotransmitters goes much further than just their involvement in synthesis, release, and reuptake. Mitochondria actually have receptors for some neurotransmitters,
neurotransmitters are much more than just messengers between cells impacting mood. They are essential regulators of metabolism and mitochondria themselves.
Mitochondria also play an essential role in immune system function.16 This includes fighting off viruses and bacteria, but it also includes low-grade inflammation, something that has been found in most metabolic and mental disorders to some degree. Mitochondria help regulate how immune cells engage with immune receptors. When cells are highly stressed, they often release components of mitochondria, which serve as a danger signal to the rest of the body, one that activates chronic, low-grade inflammation.17
We now know that mitochondria help control and coordinate the stress response in the human body. This includes both physical and mental stressors.
When cells are physically stressed, they initiate a process called the integrated stress response.
mitochondrial stress itself leads to the integrated stress response.19 If the cell isn’t able to manage the stress, one of two things happens—it either triggers its own death, a process called apoptosis, or it enters into a “zombielike” state called senescence, which has been associated with aging
“Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress.”
mitochondria are directly involved in controlling all these stress responses, and if mitochondria aren’t functioning properly, these stress responses are altered.
Mitochondria are key regulators of hormones. Cells that make hormones require more energy than most. They synthesize the hormones, package them up, and release them, just as I described for neurotransmitters.
For some hormones, mitochondria are even more important—this includes well-known names like cortisol, estrogen, and testosterone. The enzymes required for initiating the production of these hormones are found only in mitochondria. Without mitochondria, these hormones aren’t made.
When mitochondria burn fuel, electrons flow along the electron transport chain. These electrons are a source of energy usually used to make either ATP or heat. However, sometimes these electrons leak outside of the usual system. When they do, they form what are called reactive oxygen species (ROS).
small amounts of ROS actually serve a useful signaling process inside the cell.
large amounts of ROS are toxic and result in inflammation.23 You may have heard the term oxidative stress—that’s what this is!
Given that ROS are produced right in the mitochondria and are highly reactive, they often damage mitochondria first.
As well as producing ROS, mitochondria also clean up some of it up through an elaborate system of enzymes and other factors that serve to detoxify ROS.
Mitochondria change shape in response to different environmental factors.
These changes in shape are very important to cell function.
the process of mitochondria fusing with each other significantly impacts fat storage, eating behaviors, and obesity.
Mitochondrial changes in shape and their fusion with each other appear to create signals that can ...
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We now know that it’s not always about the genes themselves, but more about what causes certain genes to turn on or off. This is the field of epigenetics. Mitochondria are primary regulators of epigenetics. They send signals to the nuclear DNA in several different ways.
ratio of ATP to ADP, levels of ROS, and calcium levels can all affect gene expression.
mitochondria are required for the transport of an important epigenetic factor, nuclear protein histone H1.26 This protein helps regulate gene expression and is transported from the cytoplasm to the nucleus, a process that requires ATP. Researchers discovered, however, that ATP alone isn’t enough. Mitochondria must be present in order for this transfer to occur. Without mitochondria, this transfer doesn’t happen.
protein, GPS2, is released by mitochondria in response to metabolic stress.
another mitochondrial protein, MOTS-c, that is coded for by mitochondrial DNA and plays a role in gene expression.29
MOTS-c gets produced in response to metabolic stress as well. After MOTS-c is produced in the mitochondria, it makes its way into the nucleus and binds to the nuclear DNA. This results in the regulation of a broad range of genes—ones related to stress responses, metabolism, and antioxidant effects.
This study provided evidence that mitochondria are not just involved in the expression of genes related to energy metabolism, but possibly in the expression of all genes.
mitochondrial biogenesis. Some cells end up with a lot of mitochondria. These cells can produce more energy and function at a higher capacity. It is widely believed that the greater the number of healthy mitochondria in a cell, the healthier the cell.
mitochondria are essential to cell growth and differentiation.
Recent research, however, strongly suggests a much more active role. Their regulation of calcium levels and other signaling pathways are essential to this process.31 Their fusion with each other appears to send signals that activate genes in the nucleus. When mitochondria are prevented from fusing with each other, the cells don’t develop correctly.32 Other research has shown that mitochondrial growth and maturation is essential to proper cell differentiation.33 Still other research has shown a direct and essential role of mitochondria in the development of brain cells.34 The bottom line is
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Mitochondria appear to be in a complicated feedback cycle with autophagy, as dysfunctional mitochondria can be removed and replaced with healthy mitochondria in a process known as mitophagy.
It was once thought that genes in the nucleus controlled apoptosis. We now know that’s not true. It’s mitochondria.
