Taurine, Glutathione and Bioenergetics - Advances in Experimental Medicine and Biology - page 8

1.2.6 Controlling the Mitochondrial Inner-Membrane Potential

When accepting the hypothesis that GSH (or perhaps thiol groups in general) acts
as redox buffer for the mitochondrial matrix it also means that the thiol/disulphide
redox equilibrium is responsible for the electrical redox gradient across the mito-
chondrial inner-membrane corresponding to a potential difference D E GSH . If it is
also assumed that the redox potential in the cytosol can be considered as constant
E 0 , the electrical gradient contribution in equation (1.1) can be expressed as
D Y = D E GSH + E 0 . When adding a potential contribution D E D pH from the pH differ-
ence, it means that the potential difference D E Total (or proton-motive force) across
the mitochondrial inner-membrane can be expressed as follows:

D E =++ D E D E E

0 .

(1.6)

Total GSH D pH

As shown in Fig. 1.1 this equation makes it possible to explain that the mito-
chondrial membrane potential has been reported to be independent on the matrix pH
(see Fig. 4.5 in Bioenergetics 3, Nicholls and Ferguson 2002 ; Nicholls 1974 ) . The
higher concentration of taurine in mitochondria means that taurine acts as the pri-
mary pH buffer in the matrix, and the thiol group in GSH becomes protected from
deprotonation and to focus on being a redox buffer in the oxidative matrix environ-
ment. With taurine as pH buffer, the matrix pH must be expected to be below the
ionisation constant for the thiol group in GSH. Consequently, the mitochondrial
membrane potential will be kept almost constant (see Fig. 1.1 ).

1.3 Model for Mitochondrial Bioenergetics

A simplified model for mitochondrial bioenergetics can now be presented as in
Fig. 1.3 . The basic substrate acetyl-CoA is provided either from pyruvate oxidation
by pyruvate dehydrogenase or from beta-oxidation of fatty acids. Subsequently,
acetyl-CoA is oxidised to CO 2 with the reduction of NAD + to NADH by the tricar-
boxylic acid cycle. NADH is used by the electron transport chain to pump protons
and thus creating a mitochondrial inner-membrane proton gradient. Besides the pro-
ton pumping, NADH is also used for setting up the GSH redox equilibrium. Several
of the processes are stabilised through pH buffering by taurine.

1.4 Perspectives and Future Developments

The presented model for the mitochondrial function needs obviously to be extended
with incorporation of the complexes from the electron transport chain, and with the
formation of free radicals and ROS, which are well-known by-products from the
electron transport chain. However, although such an extension of the model is in
progress, it is by no means easily formulated. An initial observation to be included