Potential effect on weak anions distribution
The operation of the electroneutral anion carriers leads to a modest accumulation of polybasic acids (e.g. citrate) within the matrix space. In general, at equilibrium:
The carriers may not reach equilibrium if the ligand flux is high, and the pH differential may vary under physiological conditions, but as an approximate guide we would expect the following pattern:
anion | charge at pH 7.2 | ratio [in]/[out] |
pyruvate | -1 | 3 |
phosphate | -1.5 | 5 |
malate | -2 | 9 |
citrate | -3 | 27 |
This is generally helpful for the operation of the citric acid cycle, and also has implications for the regulation of glycolysis and lipogenesis by phosphofructokinase and acetyl-CoA carboxylase, where citrate is an allosteric effector.
The case of phosphate is interesting, since this anion has a pK near neutrality and a fractional charge at physiological pH values. The pH is different on the two sides of the mitochondrial inner membrane, so the ratio between singly and doubly charged phosphates will differ in the two compartments. Try to convince yourself that it makes absolutely no difference to the outcome whether phosphate is taken up as H3PO4 in exchange for nothing (i.e. a proton symport), H2PO4- in exchange for one OH- or as HPO42- in exchange for two OH- followed by appropriate re-ionisations on the inside.
Chloride in membrane potential
mitochondria CFTR
Helicobacter pylori VacA Toxin/Subunit p34: Targeting of an Anion Channel to the Inner Mitochondrial Membrane, 2010