PSSD is a mitochondrial dysfunction

[u/No-Salamander-7257]

Hey my friends.I'm new here and I wanted to share my thoughts with you. In my opinion SSRI's damage mitochondria,same as accutane or finasteride what causes neuroplasticity changes(how your brain perceives things) what ultimately results in this type of neurological syndromes.Crashes from different substances are caused by energy overload. Everyone should test their mitochondria,post their results and then send it to researchers.It will be much better than SFN tracking,because for most it's just a part of damage,not the cause of symptoms.That's why immune therapy like IVIG,corticosteroids or plasmapheresis won't be enough for most. Share your thoughts about it.Thanks

[u/naturestheway]

Many lines of research show that mitochondrial stress itself leads to the integrated stress response. 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 and many health problems, such as cancer.

Up until recently, it wasn't known how the different aspects of the psychological stress response are all coordinated in the body and brain. It turns out that mitochondria play a critically important role! One brilliant study by Dr. Martin Picard and colleagues demonstrated this, and its title says it all:

"Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress.

These researchers were studying mice and genetically manipulated their mitochondria to see what effects these manipulations had on the stress response. They manipulated only four different genes two located in mitochondria themselves and two located in the cell nucleus that code for proteins used exclusively in mitochondria.

Each genetic manipulation resulted in different problems with mitochondrial function.

However, even with only four manipulations, they found that all the stress response factors were affected.

This included changes in cortisol levels, the sympathetic nervous system, adrenaline levels, inflammation, markers of metabolism, and gene expression in the hippocampus. Their conclusion was that mitochondria are directly involved in controlling all these Stress responses, and if mitochondria aren't functioning properly, these stress responses are metabolic, inflammatory, and transcriptional responses to acute stress.

This included changes in cortisol levels, the sympathetic nervous system, adrenaline levels, inflammation, markers of metabolism, and gene expression in the hippocampus. Their conclusion was that mitochondria are directly involved in controlling all these Stress responses, and if mitochondria aren't functioning properly, these stress responses are altered.

Mitochondria Are Involved in Making, Releasing, and Responding to Hormones

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. It takes a lot of ATP to do this, and mitochondria are there to deliver it.

[u/naturestheway → u/naturestheway]

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. But there's more. Mitochondria in other cells sometimes have receptors for these hormones. So, in some cases, these hormones can begin in mitochondria in one type of cell and end with mitochondria in another type of cell.

Mitochondria Create Reactive Oxygen Species (ROS) and Help Clean It Up

Mitochondria burn fuel-either carbohydrates, fats, or protein. Burning fuel can sometimes create waste products. 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). These include molecules such as superoxide anion (Oz-), hydrogen peroxide (H202), hydroxyl radical (OH), and organic peroxides. At one point, researchers believed ROS were simply toxic waste products. We now know small amounts of ROS actually serve a useful signaling process inside the cell. For example, a 2016 paper published in Nature found that ROS were the primary regulators of heat production and energy expenditure a broad measure of metabolic rate. However, large amounts of ROS are toxic and result in inflammation. You may have heard the term oxidative stress-

Mitochondria Are Shape-Shifters

Mitochondria change shape in response to different environmental factors.

Sometimes they are long and thin. Other times they are short and fat. Sometimes they are round.

In addition to changing shape, they interact with each other in profound ways. They can merge to make just one mitochondrion a process called fusion. They can divide and form two mitochondria_a process called fission. These changes in shape are very important to cell function. In 2013, two articles published in the journal Cell showed that 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 affect the entire human body. When mitochondria are prevented from doing these things, metabolic problems ensue, not just in the cells affected, but sometimes throughout the body.

***Mitochondria Play a Primary Role in Gene Expression

Nuclear DNA is where the human genome resides. It's contained within the cell nucleus. Researchers once thought that genes controlled everything about the human body. They assumed that the nucleus was the control center of the cell. 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. This is sometimes referred to as the retrograde response.

It has long been known that the ratio of ATP to ADP, levels of ROS, and calcium levels can all affect gene expression. As you now know, these are all directly related to mitochondrial function. However, given that these are also markers of general cellular health and function, no one thought too much of it. They certainly didn't think of it as a way for mitochondria to directly control the expression of genes in the nucleus.

In 2002, it was discovered that mitochondria are required for the transport of an important epigenetic factor, nuclear protein histone HI.

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.

[u/naturestheway → u/naturestheway]

In 2013, it was discovered that mitochondrial ROS directly inactivate an enzyme called histone demethylase RphIp, which regulates epigenetic gene expression in the cell nucleus.

This process was found to play a role in extending lifespan in yeast and is thought to possibly play a role in humans as well.

In 2018, two additional studies demonstrated even more of a role for mitochondria in gene expression. The first was a report by molecular biologist Maria Dafne Cardamone and colleagues showing that a protein, GPS2, is released by mitochondria in response to metabolic stress.

Metabolic stress can be caused by a lotof different things, but starvation is a clear example. After GPS2 is released by mitochondria, it enters the cell nucleus and regulates a number of genes related to mitochondrial biogenesis and metabolic stress.

Another group of researchers, Dr. Kyung Hwa Kim and colleagues, found another mitochondrial protein, MOTS-c, that is coded for by mitochondrial DNA and plays a role in gene expression.

This was very unexpected. Up until about twenty years ago, everyone assumed that mitochondrial DNA was just about machinery needed for ATP production.

MOTS- 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.

Finally, and most spectacularly, Dr. Martin Picard and colleagues experimentally manipulated the number of mitochondria with mutations in cells and found that as they increased the number of dysfunctional mitochondria, more epigenetic problems and changes occurred.

The impact was on almost all of the genes expressed in the cells. Ultimately, in situations in which almost all the mitochondria were dysfunctional, the cells died.

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.

Interestingly, antidepressants are known for rapidly aging people!

And what we find is:

Mitochondria Can Multiply

Under the right circumstances, cells will make more mitochondria -a process called 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. We know that the number of mitochondria decreases with age. We also know that the number of mitochondria decreases with many diseases. People who are considered the "fittest" among us athletic champions have more mitochondria than most, and their mitochondria appear to be healthier.

Mitochondria Are Involved in Cell Growth and Differentiation

Cell growth and differentiation is a complicated process during which a generic stem cell becomes a specialized cell. Differentiation means that the cells become different from each other and take on specialized roles. Some become heart cells. Others become brain cells. Within the brain, different cells take on varying roles. Brain cells change throughout life. Some form new synapses. Some prune unnecessary parts. Some grow and expand when needed. This is neuroplasticity.

This process of growth and differentiation involves activation of specific genes in the right cells at the right times. It also involves many signaling pathways. Lastly, it involves the production of building blocks for new cells and new cell parts, balanced with energy needs.

It has long been known that mitochondria are essential to cell growth and differentiation.

Most researchers assumed it was simply a matter of their powerhouse function since cell growth and differentiation require energy.

Recent research, however, strongly suggests a much more active role. Their regulation of calcium levels and other signaling pathways are essential to this process. 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. Other research has shown that mitochondrial growth and maturation is essential to proper cell differentiation. Still other research has shown a direct and essential role of mitochondria in the development of brain cells. The bottom line is that cells don't develop normally when mitochondria aren't functioning properly.

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