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Mitochondrial Leakiness

Discussion in 'Beginners Area' started by QiGuy1997, Dec 13, 2013.

  1. QiGuy1997

    QiGuy1997 New Member

    I'm trying to better understand mitochondrial function, however each time I read something it seems to only further confuse the issue. If I understand Dr. Kruse's idea properly, he essentially suggests that glucose produces massive ROS (like superoxide) production in the mitochondria and that ketone/fat metabolism is preferable because it produces less ROS in the Electron Transport Chain. There are 3 major points of confusion I have.
    1. Dr. Kruse seems to suggests, in his leaky life post, benefits stemming from ROS production, such as reduced mutations and things. If this is true, then by his own theories glucose should provide see beneficial effects, right?
    2. Ketones and fats (which drive electrons through complex II) actually seem to produce far MORE ROS (in the form of superoxide) than glucose oxidation (which drives electrons through complex I).

    "Adding in glutamate mixed with malate is a classic combination for driving NADH utilisation through complex I. The mitochondria generate about 30pmol/min of H2O2 under these conditions. This is not a lot and some labs report the amount as being close to zero.
    Driving complex II (succinate dehyrdogenase) directly, using succinate but not supplying any NADH generators, produces rather more H2O2, around 400pmol/min. A ten fold increase.
    Clearly, this interferes with Dr. Kruse's idea that ketones/fat oxidation produce less ROS than glucose metabolism, right?

    3. If I'm not mistaken, Dr. Kruse believes that by decreasing the "Leakiness" of our mitochondria, we can be healthier. However, Leakiness of mitochondria (such as increase superoxide production) is what causes mitochondrial biogenesis, something we should certainly be after. So it seems like we should increase leaky mitochondria in order to create more superoxide to drive mitochondrial biogenesis.
  2. Jack Kruse

    Jack Kruse Administrator

    your missing the context..........nothing interferes. It all clicks.
  3. Jack Kruse

    Jack Kruse Administrator

    Go read Nick Lane's book Power Sex and Suicide for a primer on the context of how the mitochondria work. They are complex and counterintuitive because they are the ultimate quantum tunneler.
    Brent Patrick likes this.
  4. nonchalant

    nonchalant Silver

    I've been reading this book. Good thing Jack has already introduced us to some of the concepts, makes it easier.

    One awesome quote from p.11:
    10% of our weight in bacterial-sized units. We're crawling with mitochondria!
    Josh likes this.
  5. nonchalant

    nonchalant Silver

    And on p.15,
    Not only to antibiotics wipe out our gut microbes, they also adversely affect our mitochondria? Mitochondria don't do a lot of protein synthesis, the cell nucleus does most of the work for them. Mito do synthesize the most critical proteins for cellular respiration, though, like the proteins that start building the various complexes, like ATPase, on the inner membrane. Holy protein-folding, Batman!
    Josh likes this.
  6. caroline

    caroline Moderator

    Is that book a tough read Sally?
  7. nonchalant

    nonchalant Silver

    Not really, Audrey. Some of the concepts would be startling, but Jack has already startled us with them, so it is easy to get all the implications. But then I'm only half through... Nick Lane has a great writing style, bringing together other people's points of view and discussing them fairly, before settling on a concept. A bit like Pollack's, in that respect.
  8. caroline

    caroline Moderator

    I have sooooo much stuff I have to read...... thanks!
  9. Aerose91

    Aerose91 New Member

    Antibiotics are terrible for mitochondria. Thier toxic
  10. sam112233

    sam112233 New Member

    One of the best things to take for the mitochondria is succinic acid. It ties into complex 2 of the electron transport chain which ties complexes 1, 3, and maybe 4 together. It can cure some mitochondrial diseases.
  11. caroline

    caroline Moderator

    can we have a human pic please..... a face would be great!

    What are your qualifications for the above statement???
  12. sam112233

    sam112233 New Member

    Okay I will see if I have a pic on my computer somewhere. There is a lot of studies on succinic acid one of them shows it can cure MELAS syndrome a severe mitochondrial disease. It could treat all electron transport chain mutations except complex 2 which will be treatable with fumaric acid- another awesome organic acid. Here is a drop box file full of info on it: https://www.dropbox.com/sh/lmtgc3lumbeuivc/AAAf6x1C-hr1cMaOXGRBacO9a?dl=0

    It is messy but in the text files called succinic acid will be summaries of it. I don't think it has the diabates studies in it just google "succinate diabetes NCBI" for them, and copy paste DOI numbers into sci hub for full articles. Here is the start of one of the summaries on succinic acid:

    In Western countries, the coenzyme Q10 is very popular. In some experiments, coenzyme Q10 showed the ability to express prolonged life. But here that is interesting; There is a drug that plays in the body a role similar to coenzyme Q10. It is also, and perhaps more effective, at a price that is about 10 times cheaper. It's succinic acid. Perhaps, it is because of such a low price that amber acid is not promoted to the market.
    We should pay special attention to succinic acid (hereinafter YaK)! By the ratio of price / effectiveness, this thing is almost the leader among the means to prolong life. Yak is a natural substance (present in all organisms), has a powerful healing effect, without causing side effects and addictive. There are many reasons for this, but there are basic reasons.
    Amber acid:

    1. Stimulates the production of energy in cells. With age, in addition to other disorders, the cells of the body begin to lose the ability to generate energy. As a consequence, the body begins to lack energy for the normal provision of many of its functions, and this leads to the aging of the body and its rapid aging. The main substance in the body that gives energy is ATP (adenosine triphosphate). So, succinic acid helps to produce ATP. As a consequence, it is a powerful stimulator of energy production and a stimulator of many functions of the body, has an exceptional restorative power.
    2. Enhances cellular respiration, promotes the assimilation of oxygen by cells, tissues, organs. For example, the increase in the rate of oxygen consumption by liver cells with the addition of YaK increases 60-fold.
    3. Disinfects free radicals. Has a powerful antioxidant property. As it was said more than once, in the process of vital activity of the body aggressive forms of oxygen are formed which oxidize or destroy cells, causing diseases (cancer, heart attack, etc.), aging and death. Yak can effectively neutralize free radicals.
    In general, the effect of YaK on the body is enormous. She:

    Inside the mitochondria, succinate is one of the most prominent intermediates of the Krebs
    cycle. Succinate oxidation in mitochondria provides the most powerful energy output per
    unit time. Extra-mitochondrial succinate triggers a host of succinate receptor (SUCN1 or
    GPR91)-mediated signaling pathways in many peripheral tissues including the hypothalamus. One of the actions of succinate is to stabilize the hypoxia and cellular stress conditions by inducing the transcriptional regulator HIF-1a. Through these actions, it is hypothesized
    that succinate has the potential to restore the gradual but significant loss in functions
    associated with cellular senescence and systemic aging​

    Succinate is an essential component of the Krebs or citric acid cycle and serves an electron donor in the production of fumaric acid and FADH2. It also has been shown to be a good "natural" antibiotic because of its relative acidic or caustic nature (high concentrations can even cause burns). Succinate supplements have been shown to help reduce the effects of hangovers by activating the degradation of acetaldehyde - a toxic byproduct of alcohol metabolism - into CO2 and H2O through aerobic metabolism. Succinic acid has been shown to stimulate neural system recovery and bolster the immune system. Claims have also been made that it boosts awareness, concentration and reflexes.

    Another awesome thing I just found it is it is possible to buy ozone generator machines on ebay both the ones to ozonate water/oil, and also ones that put ozone gas out into the room. I'm going to get both to ozonate water, and also to leave the gas one running through out the night to breath it in.
  13. JanSz

    JanSz Gold

  14. sam112233

    sam112233 New Member

    Yeh they they put succinate in some medications.

    It is sold as pure succinic acid granules on amazon or ebay. 1000s of tons of it are made every year for use in industry. Ali Baba has it also.

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