#mitochondrial function

[blueoaknx]

Reclaim Vitality: The Science Behind Mitochondrial Biogenesis

Mitochondrial biogenesis is the cellular process of increasing the number of mitochondria, the organelles responsible for generating energy. This process is essential for maintaining cellular health and vitality, particularly in tissues with high energy demands, such as muscles. Mitochondrial biogenesis is often triggered by increased energy demand, usually resulting from exercise, caloric restriction, or the intake of specific nutrients.

Mitochondria are the energy producers of the cell, generating ATP, the energy currency of the cell, through oxidative phosphorylation. As cells face greater energy demands, they need more mitochondria to meet these requirements efficiently. The increase in mitochondrial numbers allows cells to produce more energy and better adapt to stress, thus enhancing overall health, recovery, and performance.

Key Factors Involved in Mitochondrial Biogenesis

Several molecular regulators drive mitochondrial biogenesis, with the most important being:

PGC-1α ActivationPGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is recognized as the master regulator of mitochondrial biogenesis. This protein plays a pivotal role in controlling the transcription of nuclear genes that encode mitochondrial proteins. When activated by external stimuli like exercise, PGC-1α interacts with transcription factors like NRF-1 and NRF-2 to drive the production of new mitochondria. This results in increased mitochondrial DNA (mtDNA) replication and the synthesis of mitochondrial proteins necessary for energy production and cellular respiration.

AMPK & SirtuinsAMPK (AMP-activated protein kinase) is another critical regulator that responds to low energy levels within the cell (a high AMP ratio). It activates PGC-1α, which, in turn, increases the number of mitochondria. AMPK is activated during energy-demanding activities such as endurance exercise and fasting. Sirtuins (SIRT1) are a class of NAD+-dependent enzymes that also regulate mitochondrial biogenesis. Sirtuins, especially SIRT1, deacetylate PGC-1α, further activating it to promote the transcription of mitochondrial genes. Both AMPK and sirtuins respond to energy deprivation, whether through physical exertion or caloric restriction, helping cells increase energy efficiency and prolong cellular longevity.

Antioxidant Defense and Cellular ResilienceOne of the benefits of mitochondrial biogenesis is the enhancement of cellular resilience through improved antioxidant defences. Mitochondria are not only energy producers but also sources of reactive oxygen species (ROS), which can damage cells if not adequately managed. By increasing the number of healthy mitochondria, cells improve their ability to manage oxidative stress. New mitochondria are typically more efficient at energy production and less likely to produce excess ROS, reducing overall cellular damage. This process helps to protect cells from age-related decline and stress-induced damage.

How Mitochondrial Biogenesis Impacts Health and Performance

Mitochondrial biogenesis is essential for maintaining optimal energy production, particularly during periods of increased physical activity or stress. In muscle cells, the increased number of mitochondria leads to improved ATP generation, enhancing endurance and reducing fatigue during prolonged exercise. This is particularly important for athletes or individuals who engage in regular physical activity, as their muscles require a constant supply of energy for performance and recovery.

For general health, mitochondrial biogenesis supports metabolic efficiency and longevity. In metabolic disorders like type 2 diabetes and obesity, mitochondrial dysfunction often results in impaired energy metabolism and increased oxidative stress. By promoting mitochondrial biogenesis, cells can restore normal mitochondrial function, improving insulin sensitivity and energy balance. Furthermore, mitochondrial biogenesis may help reduce the risk of chronic diseases related to ageing by maintaining cellular energy production and reducing oxidative stress.

Beyond exercise and metabolic health, mitochondrial biogenesis is also a key factor in the body’s ability to adapt to various stressors, whether environmental or nutritional. The increase in mitochondrial capacity allows cells to better handle changes in energy demand, supporting recovery and cellular adaptation. For instance, during periods of caloric restriction, mitochondrial biogenesis helps the body use energy more efficiently, contributing to longer-term health benefits, including improved longevity and resistance to age-related diseases.

Supporting Mitochondrial Biogenesis with Nutraceuticals

In addition to lifestyle factors like exercise and caloric restriction, certain nutraceuticals can support mitochondrial biogenesis. Mitokatlyst™-E is one such product that targets mitochondrial function, optimising energy production, and promoting muscle recovery. By stimulating the molecular pathways involved in mitochondrial biogenesis, such products can enhance the body’s ability to adapt to stress, recover more efficiently, and improve overall cellular function.

Conclusion

Mitochondrial biogenesis is a vital process that supports energy production, cellular health, and adaptability to environmental and physical stressors. By regulating pathways such as PGC-1α, AMPK, and sirtuins, cells can increase mitochondrial content to meet higher energy demands, promote muscle recovery, and improve overall vitality. Products like Mitokatlyst™-E are designed to optimise mitochondrial function, helping the body adapt to stress and maintain optimal cellular health. By supporting mitochondrial biogenesis, we can improve energy efficiency, enhance physical performance, and promote long-term health and resilience.

[mehmetyildizmelbourne-blog]

Boosting Mitochondrial Health: How to Tame Chronic Inflammation with DAMPs Know-How

Exploring Mitochondrial Damage Signals and Practical Steps to Reduce Inflammation for Optimal Cellular Health I talk a lot about Mitochondria, as they matter. Every cell needs them, and their dysfunction is associated with all metabolic diseases, cancers, and neurodegenerative disorders. They are extra critical for energy organs like the brain and the heart. So, if our mitochondria malfunction,…

[haggishlyhagging]

Because I feel that I am a woman, therefore you must treat me as if I actually am, otherwise you are transphobic. As I insist on participating as a woman in your groups, gatherings, or spaces you also must forgo discussing anything about your female socialization, female anatomy, or female functions because it hurts my feelings. It hurts my feelings because I was neither socialized as a girl nor am I capable of experiencing what the female body experiences from cradle to grave. But if you speak about this I am then reminded that I am not female, and therefore not really a woman. My experience of feeling like a woman must not be invalidated by your experiences of being a woman, therefore I will shame you for being female, teach you in university to estrange your body from your mind, make your distinct physicality and oppression that is specific to your sex irrelevant in the laws of the land or anything that names our differences until there is only the mind. Now only how I think about your body is real. Mind over body. Mind over matter. Spirit over matter/mater/mother. A woman is anyone who says they are a woman. My word is now more real than your mitochondrial DNA. Accept that by my word, you really don't exist.

-Ruth Barrett, “Gyn-ocide Revisited” in Female Erasure

[mindblowingscience]

Researchers at the Department of Cell and Molecular Biology, Karolinska Institutet have made a major discovery in how human cells produce energy. Their study, published in The EMBO Journal, reveals the detailed mechanisms of how mitochondria process transfer RNA (tRNA) molecules, which are essential for energy production. Mitochondria need properly processed tRNAs to make proteins for energy. Problems in tRNA processing can lead to serious mitochondrial diseases. Until now, the exact process of tRNA maturation in mitochondria was not well understood. "Our study reveals, at a molecular level, how the mitochondrial RNase Z complex recognizes and processes tRNA molecules," said Genís Valentín Gesé, the first author of the study. "By using advanced cryo-electron microscopy, we've been able to visualize the complex in action, capturing snapshots of tRNA at different stages of maturation. This is a significant step forward in understanding how our cells produce energy and maintain healthy function."

Continue Reading.

[transmutationisms]

these tags annoyed me to be honest

1. PCOS is a bad point of comparison because despite the name, diagnosis is not *supposed to be* done on the primary basis of finding cysts in the ovaries; these are common and not inherently of concern. instead, the more indicative biomarker is the hormone test (high levels of testosterone *throughout the menstrual period*, with corresponding disruption to the expected/typical fluctuations in estrogen/progesterone) but often diagnosis is done more on the basis of a physical exam ('exam') confirming characteristics such as hairiness or adiposity. this absolutely DOES result in PCOS overdiagnosis for some demographics; while a real biological condition, PCOS is also a load-bearing diagnostic term in the enforcement of very specific standards of (white) femininity and its use also frequently masks, for example, the frequency of hypothalamic amenorrhea (HA) secondary to chronic energy deficiency (as in anorexia), which doctors are loathe to diagnose because they view weight loss as prima facie good

2. the reason it matters that psychiatric diagnoses do not have a 'biology' is not because every disease must have a single specific biomarker; it is correct that some do not. however, the way patient complaints are sifted into categories labelled 'psychiatric' versus '(otherwise) medical' begins essentially with determining whether the distress is 'physical' or 'mental'. in other words, in the case of, say, the chronic fatigue syndrome (famously, lacking a known specific biomarker), the symptoms being investigated by the non-psychiatrist physician are still physical (PEM; mast cell dysregulation; pain; etc) whereas a diagnosis of depression may be accompanied by, but requires no, physical symptoms or presentation. the psychiatric claim that its diagnoses have biological causes and correlates is specifically a claim about the role of neurobiology in the causation of affective states; thus, the comparison to physical complaints is meaningless here

3. this person goes on to claim that depressives do in fact share, though not universally, certain biomarkers such as mitochondrial dysregulations. such claims typically come from various imaging studies plagued with systemic problems in the selection and definition of patient populations as well as the subjectivity of result interpretation and analysis. these claims are not well supported and typically rely on circular selection and definition of patient populations

4. speaking philosophically, it is in fact often correct to challenge the notion that a physical 'disease' chronically lacking a specific biomarker is indeed a disease, in any sense besides the colloquial one. that is, diseases that cannot be correlated with one cause or presentation are often better understood as 'syndromes', which is to say, as a taxonomical heuristic that is likely grouping together multiple disparate physical (anatomical, physiological, functional, &c) problems with multiple disparate causes. this is almost certainly the case for chronic fatigue syndrome, for example. this is a philosophical distinction that matters for research and understanding, and does not mean or imply anything to minimise or contradict the patient experience of the syndrome or symptoms. it matters because, for instance, CFS triggered by the epstein-barr virus may indeed turn out to have different disease mechanisms to CFS triggered by, say, covid-19, or may have different specific mechanisms when running in certain families, and so on. distinguishing these much more specific presentations, and possibly distinct diseases, from the current discursive schema of the overlying syndrome is potentially very good for patients, who likely have different needs and treatments to one another despite currently all sharing the same label in their charts

5. which goes back to an overlying point, which is that (despite frequent defensiveness to the contrary), whether or not something is a disease does not inherently tell us anything about its reality, its severity, its cause, the moral status of its sufferers, &c

[foxgirlinfohazard]

new fetish: mitochondrial vore. the prey is eaten by the pred and instead of being digested they add a useful function to the pred while being trapped inside them

[willowreader]

Excellent article from a scientist who does great research and has her own lab.

[covid-safer-hotties]

Also preserved in our archive

Listen at the first link!

The GIST

Recent studies suggest that a hypermetabolic state that damages the mitochondria results in a hypometabolic state in chronic fatigue syndrome (ME/CFS), long COVID, and fibromyalgia (FM). They also suggest that something in the blood, serum, or plasma is damaging the mitochondria in these diseases.

We’re not done with the mitochondria, though – far from it! Now we look at a bevy of recent long-COVID mitochondrial studies suggesting that mitochondrial dysfunction affects more than energy production and which illuminate what may have gone wrong in the mitochondria.

Muscle biopsies of 120 long-COVID patients who had ended up in the ICU found that a year later their muscles had higher levels of immune cells involved in tissue repair and reduced activity of the 2nd and fourth mitochondrial complexes. The authors concluded that there was “aberrant repair and altered mitochondrial activity in skeletal muscle.”

They couldn’t explain how a respiratory illness affected the muscles but a subsequent study did. A hamster model found that the coronavirus suppressed the genes associated with the muscle fibers, protein production, both sides of the mitochondrial energy production process (Krebs cycle and electron transport chain), and fat breakdown.

As it was doing that, it unleashed a barrage of inflammatory factors (IFN-α, IFN-γ, and TNF-α) which triggered a shift from relying mostly on aerobic energy production to the less effective process of anaerobic energy production (glycolysis).

The authors concluded that using treatments “that can boost mitochondrial functions, enhance protein synthesis, and inhibit protein degradation” may be useful for treating muscle fatigue in long COVID.

Next, a muscle study assessing “maximal fatty acid oxidation (MFO)” (i.e. energy produced by the breakdown of fats during exercise) found significantly reduced levels of fatty acid oxidation in long COVID and a “premature shift” from relying on fats to carbohydrates to powering their cells.

This was important because the body prefers to burn fats during exercise and because fats play key roles in both parts of the mitochondrial energy production process. The finding wasn’t so surprising, though. Problems with carnitine – which transports fatty acids into the mitochondria – have popped up in both long COVID and ME/CFS – suggesting that the fatty acids that power the mitochondria during exercise may not be getting into them.

A review paper asserted that increased free radical production (reactive oxygen species (ROS)) by the mitochondria both pushes the cell into a state of anaerobic energy production but also pushes the immune system to activate the inflammatory or innate immune response and away from the adaptive immune response that targets pathogens. This benefits the viruses by providing the substrates they need to grow and allows them to escape from the immune system.

Several researchers, including Avindra Nath, believe that the immune system tries to compensate for the impaired adaptive immune defense by ramping up the innate immune response. Nath believes this shift plays a central role in ME/CFS.

They proposed that treatments to boost mitochondrial functioning and reduce the production of mitochondrial reactive oxygen species (ROS) (free radicals) will be beneficial.

Lastly, a review asserted that the predominant view of the mitochondria as the main energy producers of the cell is misguided and incomplete. Harkening back to Naviaux’s characterization of the mitochondria as the primary threat-sensing part of the cell, the authors believe the mitochondria regulate the “physiological processes at the level of the cell, organ and organism”; i.e. the mitochondrial problems affect much more than low energy levels and fatigue.

A blog on red light/infrared light therapy – which could both boost mitochondrial health and antioxidant defenses – is coming up.

Full text at either link! There's a lot more than the gist

[transgenderer]

So I'm birds the heterogamous sex is the female, males have ZZ chromosomes and females have ZW chromosomes. Some of the key respiratory proteins are on the Z chromosome, so all the genes for them come from the father, but the mitochondria come from the mother. Therefore, the mother must be unusually selective in mates, if she picks a mate with bad respiratory proteins, or proteins that don't match her mitochondria, her female offspring will all die. And it seems this might explain bright plumage in male birds! Plumage patterns are sensitive to differences between groups, signalling mismatch, and it turns out bright red color reflects mitochondria functionality!

[blueoaknx]

The Impact of High Fructose Corn Syrup on Mitochondrial Function

The Impact of High Fructose Corn Syrup on Mitochondrial Function:

Analysis

High fructose corn syrup (HFCS), a widely used sweetener derived from corn, has become a major component of the modern diet, especially in processed foods and sugary beverages. HFCS is composed of glucose and fructose in varying proportions, with HFCS-55 (55% fructose, 45% glucose) and HFCS-42 (42% fructose, 58% glucose) being the most common formulations. While the impact of HFCS on metabolic health has been widely discussed, recent studies have shown that it can also exert a detrimental effect on mitochondrial function. This technical analysis explores the biochemical mechanisms by which HFCS damages mitochondria, contributing to cellular dysfunction and a range of metabolic diseases.

Mitochondrial Physiology and Biochemical Function

Mitochondria are highly specialized organelles responsible for producing adenosine triphosphate (ATP), the primary energy currency of the cell, through oxidative phosphorylation (OXPHOS). This process occurs in the inner mitochondrial membrane and involves the electron transport chain (ETC) and ATP synthase. The mitochondria are also involved in regulating cellular metabolism, maintaining redox balance, calcium homeostasis, and apoptosis (programmed cell death). Mitochondrial dysfunction, characterized by impaired ATP production, altered mitochondrial dynamics (fusion/fission), and excessive reactive oxygen species (ROS) production, is a key factor in the pathogenesis of many chronic diseases, including obesity, insulin resistance, cardiovascular diseases, and neurodegenerative disorders.

Fructose Metabolism and Its Divergence from Glucose

The metabolism of fructose, particularly in the liver, diverges significantly from that of glucose, and it is this divergence that underpins much of the mitochondrial dysfunction associated with HFCS consumption. Unlike glucose, which is predominantly metabolized via glycolysis and the citric acid cycle (TCA cycle), fructose bypasses the rate-limiting step of glycolysis, catalyzed by phosphofructokinase-1 (PFK-1), and is instead phosphorylated by fructokinase to form fructose-1-phosphate. This rapid metabolism of fructose in the liver can overwhelm metabolic pathways and lead to the accumulation of intermediate metabolites such as dihydroxyacetone phosphate (DHAP) and glyceraldehyde, which can be further converted to fatty acids and triglycerides through de novo lipogenesis (DNL).

Excessive fructose consumption leads to the accumulation of triglycerides, particularly within hepatocytes, which is a hallmark of non-alcoholic fatty liver disease (NAFLD). The lipid accumulation in the liver, in turn, exacerbates mitochondrial dysfunction and oxidative stress, contributing to insulin resistance and a cascade of metabolic disorders.

Mechanisms of Mitochondrial Damage Induced by HFCS

Increased ROS Production

One of the most significant consequences of excess fructose metabolism is the elevated production of reactive oxygen species (ROS). ROS are byproducts of cellular respiration, primarily generated at complexes I and III of the electron transport chain. Under normal conditions, mitochondria have a robust antioxidant defense system, including enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase, which help neutralize ROS. However, when cells are exposed to an overload of fructose, the liver mitochondria become overwhelmed, leading to excessive ROS generation.

Fructose metabolism increases the NADPH/NADP+ ratio, enhancing the activity of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidases such as NADPH oxidase (NOX), which further amplifies ROS production. These ROS cause oxidative damage to mitochondrial DNA (mtDNA), lipids in the mitochondrial membranes, and mitochondrial proteins. Such damage impairs mitochondrial function by decreasing mitochondrial membrane potential, disrupting the electron transport chain, and promoting mitochondrial fragmentation. Furthermore, mtDNA is particularly vulnerable to ROS due to its proximity to the electron transport chain and the lack of histone protection, leading to mutations that impair mitochondrial replication and protein synthesis.

Disruption of Mitochondrial Biogenesis

Mitochondrial biogenesis refers to the process by which new mitochondria are synthesized within a cell to meet the energy demands. This process is tightly regulated by several transcription factors, most notably peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). PGC-1α activates the transcription of nuclear and mitochondrial genes involved in energy metabolism, mitochondrial dynamics, and antioxidant defenses.

Fructose consumption has been shown to inhibit PGC-1α expression in both liver and skeletal muscle cells. Reduced PGC-1α levels lead to impaired mitochondrial biogenesis, which limits the ability of cells to adapt to increased energy demands. This is particularly concerning in tissues with high metabolic demands, such as muscle, heart, and liver, where impaired mitochondrial function can exacerbate energy deficits and lead to insulin resistance, fatty liver disease, and other metabolic disorders.

Mitochondrial Permeability Transition and Apoptosis

Chronic exposure to high levels of fructose can lead to mitochondrial permeability transition (MPT), a process in which the mitochondrial inner membrane becomes permeable to ions and small molecules, disrupting mitochondrial function. MPT is typically induced by excessive ROS production, calcium overload, or changes in the mitochondrial membrane potential. The opening of the mitochondrial permeability transition pore (MPTP) leads to the loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation, and the release of pro-apoptotic factors such as cytochrome c into the cytoplasm. This, in turn, activates the caspase cascade, promoting apoptosis.

In the context of HFCS-induced mitochondrial dysfunction, increased ROS and altered metabolic intermediates, such as ceramides, may trigger MPT and apoptotic pathways, leading to cell death and tissue damage. In tissues such as the liver and pancreas, this can exacerbate the pathological progression of fatty liver disease and insulin resistance.

Fatty Acid Accumulation and Impaired Beta-Oxidation

Excessive fructose consumption induces de novo lipogenesis (DNL) in the liver, leading to an increase in the synthesis of fatty acids, which are esterified into triglycerides and stored within hepatocytes. This accumulation of lipids can overwhelm the capacity of mitochondria to oxidize these fatty acids via beta-oxidation, leading to mitochondrial dysfunction. The accumulation of lipotoxic intermediates such as ceramides and diacylglycerols further impairs mitochondrial function by inhibiting key enzymes involved in mitochondrial energy production.

Moreover, the excess fatty acids can impair mitochondrial membrane fluidity, reducing the efficiency of oxidative phosphorylation. The lipid-induced mitochondrial dysfunction leads to further oxidative stress, creating a feedback loop that exacerbates the metabolic disturbances caused by high fructose intake.

Clinical Implications of HFCS-Induced Mitochondrial Dysfunction

The long-term consumption of HFCS has profound implications for human health, particularly in the context of metabolic diseases:

Insulin Resistance and Type 2 Diabetes: HFCS-induced mitochondrial dysfunction, particularly in liver and muscle cells, contributes to impaired insulin signaling and glucose homeostasis. As mitochondrial function declines, cells become less responsive to insulin, leading to insulin resistance, a precursor to type 2 diabetes.

Non-Alcoholic Fatty Liver Disease (NAFLD): The accumulation of fat in the liver, driven by increased fructose metabolism, leads to mitochondrial damage and dysfunction, which exacerbates the progression of NAFLD to non-alcoholic steatohepatitis (NASH), a more severe form of liver disease.

Cardiovascular Disease: Mitochondrial dysfunction in cardiomyocytes can impair ATP production, leading to reduced contractile function and the progression of cardiovascular disease. The increased oxidative stress and inflammatory mediators associated with mitochondrial damage also contribute to vascular injury and atherosclerosis.

Neurodegenerative Diseases: Impaired mitochondrial function in neurons, driven by high fructose intake, may contribute to neurodegenerative diseases such as Alzheimer's and Parkinson's disease, as mitochondria play a critical role in maintaining neuronal health.

Conclusion

High fructose corn syrup exerts a significant impact on mitochondrial function through several interconnected mechanisms. These include the increased production of reactive oxygen species (ROS), inhibition of mitochondrial biogenesis, induction of mitochondrial permeability transition, and the accumulation of toxic lipid intermediates. These disruptions in mitochondrial homeostasis contribute to the development of insulin resistance, non-alcoholic fatty liver disease, and other chronic metabolic diseases. Addressing the widespread consumption of HFCS and reducing dietary fructose intake could be crucial in mitigating mitochondrial dysfunction and preventing associated metabolic disease

[tulipscomeinallsortsofcolors]

so what im getting is that trudi is the most emotionally competent and functional person in this family for Multiple generations. love that for her honestly she deserves it

toby's genes were enough to produce one (1) half-chill person but could not stand up to gretas mitochondrial DNA any longer than that

[mehmetyildizmelbourne-blog]

How Does Ketosis Impact Mitochondrial Health?

An overview of mitochondrial bioenergetics activation with practical tips Ketosis can induce changes in metabolism, leading to increased production of ketone bodies, such as beta-hydroxybutyrate, acetoacetate, and acetone. These ketone bodies can serve as alternative energy substrates for cells, particularly in tissues or organs with high energy demands, such as the brain. Ketones are…

[darkmaga-returns]

Endocrine-disrupting chemicals and electromagnetic fields from devices like cellphones and Wi-Fi routers pose significant risks to mitochondrial function. Restoring cellular health involves eliminating toxins, adopting a whole foods diet, optimizing sun exposure and addressing gut health imbalances.

by Dr. Joseph Mercola

December 9, 2024

[briarpatch-kids]

Denied again by social security. I don't get how they expected me to work with a 70% mental health rating by the military and fucking mitochondrial myopathy.

Like this is the requirement for 70% mental health rating:

70% rating: The veteran is unable to function in most social and work areas with symptoms such as:

obsessive behaviors

illogical speech

persistent severe depression and panic

suicidal thinking

inability to control impulses (including becoming violent without provocation)

neglecting self-care such as basic hygiene

inability to handle stress, and

being unable to maintain relationships.