Essential Cell Biology 5th edition

Mitochondria and Oxidative Phosphorylation
465
proton-motive
force due to
INTERMEMBRANE membrane potential
SPACE
+ + + + + + +
+ +
inner
mitochondrial
membrane
_ _ _ _ _ _
_ _
MATRIX
electrochemical
H + gradient
ΔV ΔV +
ΔpH
proton-motive force
proton-motive
force due to
pH gradient
H + H + H +
H +
H + H + H+ H +
H+ H + H + H +
H +
H + H +
ΔpH
pH 7.2
pH 7.9
Figure 14–15 The electrochemical H +
gradient across the inner mitochondrial
membrane includes a large force due
to the membrane potential (∆V ) and a
smaller force due to the H + concentration
gradient—that is, the pH gradient (∆pH).
The intermembrane space is slightly more
acidic than the matrix, because the higher
the concentration of protons, the more
acidic the solution (see Panel 2−2,
pp. 68−69). Both the membrane potential
and the pH gradient combine to generate
the proton-motive force, which pulls H +
back into the mitochondrial matrix. The
exact, mathematical relationship between
these forces is expressed by the Nernst
equation (see Figure 12−24).
would simply be liberated as heat. Cells are able to recover much of
this energy because each of the respiratory enzyme complexes in the
electron-transport chain uses it to pump protons across the inner mitochondrial
membrane, from the matrix into the intermembrane space (see
Figure 14–14). Later, we will outline the molecular mechanisms involved.
For now, we focus on the consequences ECB5 e14.15/14.15 of this nifty maneuver. First, the
pumping of protons generates an H + gradient—or pH gradient—across
the inner membrane. As a result, the pH in the matrix (around 7.9) is
about 0.7 unit higher than it is in the intermembrane space (which is 7.2,
the same pH as the cytosol). Second, proton pumping generates a voltage
gradient—or membrane potential—across the inner membrane; as
H + flows outward, the matrix side of the membrane becomes negative
and the side facing the intermembrane space becomes positive.
As discussed in Chapter 12, the force that drives the passive flow of an ion
across a membrane is proportional to the ion’s electrochemical gradient.
The strength of that electrochemical gradient depends both on the voltage
across the membrane, as measured by the membrane potential, and
on the ion’s concentration gradient (see Figure 12−5). Because protons
are positively charged, they will more readily cross a membrane if there
is an excess of negative charge on the other side. In the case of the inner
mitochondrial membrane, the pH gradient and membrane potential work
together to create a steep electrochemical proton gradient that makes it
energetically very favorable for H + to flow back into the mitochondrial
matrix. The membrane potential contributes significantly to this protonmotive
force, which pulls H + back across the membrane; the greater the
membrane potential, the more energy is stored in the proton gradient
(Figure 14–15).
QUESTION 14–3
When the drug dinitrophenol (DNP)
is added to mitochondria, the inner
membrane becomes permeable
to protons (H + ). In contrast, when
the drug nigericin is added to
mitochondria, the inner membrane
becomes permeable to K + . (A) How
does the electrochemical proton
gradient change in response to
DNP? (B) How does it change in
response to nigericin?
ATP Synthase Uses the Energy Stored in the
Electrochemical Proton Gradient to Produce ATP
If protons in the intermembrane space were simply allowed to flow back
into the mitochondrial matrix, the energy stored in the electrochemical
proton gradient would be lost as heat. Such a seemingly wasteful
process allows hibernating bears to stay warm, as we discuss further in
How We Know (pp. 476–477). In most cells, however, the electrochemical
proton gradient across the inner mitochondrial membrane is used to
drive the synthesis of ATP from ADP and P i (see Figure 2−27). The device
that makes this possible is ATP synthase, a large, multisubunit protein
embedded in the inner mitochondrial membrane.
ATP synthase is of ancient origin; the same enzyme generates ATP in the
mitochondria of animal cells, the chloroplasts of plants and algae, and