Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

760 Chapter 14: Energy Conversion: Mitochondria and Chloroplasts
Mitochondria are critical for buffering the redox potential in the cytosol. Cells
need a constant supply of the electron acceptor NAD + for the central reaction in
glycolysis that converts glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate
(see Figure 2–48). This NAD + is converted to NADH in the process, and the NAD +
needs to be regenerated by transferring the high-energy NADH electrons somewhere.
The NADH electrons will eventually be used to help drive oxidative phosphorylation
inside the mitochondrion. But the inner mitochondrial membrane
is impermeable to NADH. The electrons are therefore passed from the NADH to
smaller molecules in the cytosol that can move through the inner mitochondrial
membrane. Once in the matrix, these smaller molecules transfer their electrons to
NAD + to form mitochondrial NADH, after which they are returned to the cytosol
for recharging—creating a so-called shuttle system for the NADH electrons.
In addition to ATP, biosynthesis in the cytosol requires both a constant supply
of reducing power in the form of NADPH and small carbon-rich molecules
to serve as building blocks (discussed in Chapter 2). Descriptions of biosynthesis
often state that the needed carbon skeletons come directly from the breakdown
of sugars, whereas the NADPH is produced in the cytosol by a side pathway
for the breakdown of sugars (the pentose phosphate pathway, an alternative to
glycolysis). But under conditions where nutrients abound and plenty of ATP is
available, mitochondria help to generate both the reducing power and the carbon-rich
building blocks (the “carbon skeletons” in Panel 2–1, pp. 90–91) needed
for cell growth. For this purpose, excess citrate produced in the mitochondrial
matrix by the citric acid cycle (see Panel 2–9, pp. 106–107) is transported down
its electrochemical gradient to the cytosol, where it is metabolized to produce
essential components of the cell. Thus, for example, as part of a cell’s response
to growth signals, large amounts of acetyl CoA are produced in the cytosol from
citrate exported from mitochondria, accelerating the production of the fatty acids
and sterols that build new membranes (described in Chapter 10). Cancer cells are
frequently mutated in ways that enhance this pathway, as part of their program of
abnormal growth (see Figure 20–26).
The urea cycle is a central metabolic pathway in mammals that converts the
ammonia (NH 4 + ) produced by the breakdown of nitrogen-containing compounds
(such as amino acids) to the urea excreted in urine. Two critical steps of the urea
cycle are carried out in the mitochondria of liver cells, while the remaining steps
occur in the cytosol. Mitochondria also play an essential part in the metabolic
adaptation of cells to different nutritional conditions. For example, under conditions
of starvation, proteins in our bodies are broken down to amino acids, and
the amino acids are imported into mitochondria and oxidized to produce NADH
for ATP production.
The biosynthesis of heme groups—which, as we shall see in the next section,
play a central part in electron transfer—is another critical process that is shared
between the mitochondrion and the cytoplasm. Iron–sulfur clusters, which are
essential not only for electron transfer in the respiratory chain (see p. 766), but
also for the maintenance and stability of the nuclear genome, are produced in
mitochondria (and chloroplasts). Nuclear genome instability, a hallmark of cancer,
can sometimes be linked to the decreased function of cellular proteins that
contain iron–sulfur clusters.
Mitochondria also have a central role in membrane biosynthesis. Cardiolipin
is a two-headed phospholipid (Figure 14–11) that is confined to the inner mitochondrial
membrane, where it is also produced. But mitochondria are also a major
source of phospholipids for the biogenesis of other cell membranes. Phosphatidylethanolamine,
phosphatidylglycerol, and phosphatidic acid are synthesized in
the mitochondrion, while phosphatidylinositol, phosphatidylcholine, and phosphatidylserine
are primarily synthesized in the endoplasmic reticulum (ER). As
described in Chapter 12, most of the cell’s membranes are assembled in the ER.
The exchange of lipids between the ER and mitochondria is thought to occur at
special sites of close contact (see Figure 14–7) by an as-yet unknown mechanism.
O
H 2 C
O
P
O
C
O
O
H
C
OH
CH 2
CH 2 CH
O
fatty acid tail
O
C
fatty acid tail
O
O
CH 2
O
P
O
C
O
O
CH 2
CH 2 CH
O
fatty acid tail
O
C
fatty acid tail
Figure 14–11 The structure of
cardiolipin. Cardiolipin consists of two
covalently linked phospholipid units, with a
total of four rather than the usual two fatty
acid chains (see Figure 10–3). Cardiolipin
is only produced in the mitochondrial inner
membrane, where it interacts closely with
membrane proteins involved in oxidative
phosphorylation and atp transport. In
cristae, its two MBoC6 juxtaposed m14.65/14.11 phosphate
groups may act as a local proton trap on
the membrane surface.
O