Oxidized linoleic acid in cardiolipin creates leaky pores in the inner mitochondrial membrane, hindering ATP synthesis.

“cardiolipin fatty acid composition is determined in part by the diet it's also determined by dna but it's determined in part by the diet and importantly for our discussion here if you increase your linoleic acid composition you will change the composition of your cardiolipin in a lot of different tissues towards a more omega-6 fatty acid composition”

“we know that the on a very short-term diet of high omega-6 in um rodents that the cardiolipin will go down uh but you know but to one tenth of I think it's one-tenth or one-fifth of what it was um so it's destroyed really”

“but if you consume a high omega-6 diet what happens is this begins what I call a catastrophic lipid proximation Cascade and one of the things that gets oxidized in that is the linoleic acid that is in the cardiolipid”

“and then those Tails can no longer fit together properly because either the LA is oxidized or when it's oxidized it'll be replaced by other molecules like DHA or which is Diet uh the glucosa hexanoid enoic acid or arachidonic acid AA and either way if they're replaced now those molecules don't fit together properly they have this 3D conformational change and now you have you can create pores leaky spots in that inner mitochondrial membrane where the hydrogen protons can leak through and if they leak through now they can no longer create energy because they normally are going to come through the ATP synthase and that that hydrogen proton is going to provide the energy to phosphorylate ADP to ATP now you've lost that”

“and we know that the on a very short-term diet of high omega-6 in um rodents that the cardiolipin will go down uh but you know but to one tenth of I think it's one-tenth or one-fifth of what it was um so it's destroyed really and in the process um you destroy the energy making um uh capability of the mitochondria because you've you've broken down the electron transport chain which is where all”

“just like the membranes when we're consuming more unsaturated fats more polyunsaturated fats more Omega sixes more more linolic acid the composition of the cardiol lipin shifts and incorporates more of those fatty acids now in the same way that these are incredibly unstable and susceptible to oxidation if we were to cook with them or fry food with them or just have them in our bodies at 98 degrees Fahrenheit with all the oxygen running around around and whatnot this if we we are essentially putting this inside as you said a battery where we are the mo if something's going to get damaged it's there there's a lot of electrical current there's a lot of oxygen available you know we're trying to produce energy in this Factory or in this engine that's not a place where you want really unstable fats and so as the the composition of cardiolipin shifts it becomes more susceptible to peroxidation to damage and that directly impairs the function at the electron transport chain and impairs energy production ATP production and we see this when we consume or you know when they test in animals that it'll it'll shift the cardiol lipin composition and lead to more damage there and then lead to impaired ATP production impaired mitochondrial respiration”

“because of the instability of these fats when they're used as structural components in these membranes as fats as phospholipids they are more permeable to various things Crossing through the membrane and this is specifically going to be different ions like sodium and potassium as well as the hydrogen ion or proton and so this has a number of effects for one I think we'll start at the proton so the main way that we produce the actual ATP has to do with creating a proton gradient at the electron transport chain inside the mitochondria at the inner mitochondrial membrane that proton gradient depends on us being able to essentially pump a lot of protons to one side of this membrane and use the the difference in charge as a way to then produce ATP we use that as as energy when the structure of this membrane has more polyunsaturated fats it's more permeable to the protons so instead of maintaining this really strong gradient with all this energy the protons leak through the membrane so we're trying to produce all this ATP but we're not able to to create a strong enough gradient to produce as much and it and it reduces Energy Efficiency dramatically the prod the efficiency of energy production”

“because of the instability of these fats when they're used as structural components in these membranes as fats as phospholipids they are more permeable to various things Crossing through the membrane and this is specifically going to be different ions like sodium and potassium as well as the hydrogen ion or proton and so this has a number of effects for one I think we'll start at the proton so the main way that we produce the actual ATP has to do with creating a proton gradient at the electron transport chain inside the mitochondria at the inner mitochondrial membrane that proton gradient depends on us being able to essentially pump a lot of protons to one side of this membrane and use the the difference in charge as a way to then produce ATP we use that as as energy when the structure of this membrane has more polyunsaturated fats it's more permeable to the protons so instead of maintaining this really strong gradient with all this energy the protons leak through the membrane so we're trying to produce all this TP but we're not able to to create a strong enough gradient to produce as much and it and it reduces Energy Efficiency dramatically”