The principal mitochondrial K+ uniport is associated with respiratory complex I is an interesting preprint that has been withdrawn "due to disagreement with UCSF over data rights. This withdrawal decision is not related to the validity of the data presented in this study, and these authors understand that this work cannot be cited as reference for the project until the disagreement is resolved."
It remains, however, interesting. The reason I find it interesting is that there is clear evidence that there is a link between the delta pH between the mitochondrial matrix and Intermembrane Space and the mitochondrial membrane potential. This was evidenced in experiments which varied one and saw the proton motive force (which is the total of the two adjusted for the same units) remain essentially constant. Furthermore it seems that where Potassium Ion transport changes with age we can also see a reduction in the membrane potential, but an increase in delta pH. This is significant because it would drive the matrix to be more basic and the consequential changes in citrate efflux would be significant (because of the changes of the ratio between the 2- and 3- citrate species - Henderson-Hasselbalch).
Coming back to my usual hobby horse, which is citrate efflux, it seems clear that the acetyl-CoA used for acetylation of nuclear proteins is primarily converted from citrate in the nucleus rather than in the cytosol. This is why there is a disconnect between the use of acetyl-CoA in the cytosol for lipids and cholesterol and that in the nucleus. Hence a temporary increase in cytosolic citrate can be metabolised by cytosolic ACLY and stored away as lipids or cholesterol, but a steady state acetylation level in the nucleus will be maintained by the expression of ACYL which has been translocated to the nucleus (and kept there by acetylation itself).
I was wondering how the cell handled acetyl-CoA metabolism dividing it between cytosolic and nuclear and the answer is that it doesn't. Instead it transfers citrate to the nucleus and keeps essentially separate pools of acetyl-CoA.
What also seem likely is that some mutations to mitochondrial DNA affect the mitochondria through changes to the Potassium ion handling. It is still not settled science, however.
It remains, however, interesting. The reason I find it interesting is that there is clear evidence that there is a link between the delta pH between the mitochondrial matrix and Intermembrane Space and the mitochondrial membrane potential. This was evidenced in experiments which varied one and saw the proton motive force (which is the total of the two adjusted for the same units) remain essentially constant. Furthermore it seems that where Potassium Ion transport changes with age we can also see a reduction in the membrane potential, but an increase in delta pH. This is significant because it would drive the matrix to be more basic and the consequential changes in citrate efflux would be significant (because of the changes of the ratio between the 2- and 3- citrate species - Henderson-Hasselbalch).
Coming back to my usual hobby horse, which is citrate efflux, it seems clear that the acetyl-CoA used for acetylation of nuclear proteins is primarily converted from citrate in the nucleus rather than in the cytosol. This is why there is a disconnect between the use of acetyl-CoA in the cytosol for lipids and cholesterol and that in the nucleus. Hence a temporary increase in cytosolic citrate can be metabolised by cytosolic ACLY and stored away as lipids or cholesterol, but a steady state acetylation level in the nucleus will be maintained by the expression of ACYL which has been translocated to the nucleus (and kept there by acetylation itself).
I was wondering how the cell handled acetyl-CoA metabolism dividing it between cytosolic and nuclear and the answer is that it doesn't. Instead it transfers citrate to the nucleus and keeps essentially separate pools of acetyl-CoA.
What also seem likely is that some mutations to mitochondrial DNA affect the mitochondria through changes to the Potassium ion handling. It is still not settled science, however.
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