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chapter 14
Electron Transport and Oxidative Phosphorylation
C y to p la s m
M atrix
1 a n d 3 . Malate dehydrogenase
2. Malate- oc-ketoglutarate translocase
4 and 6. Aspartate aminotransferase
5. Glutamate-aspartate translocase
FIGURE 14-22
Malate-aspartate shuttle for the transport of cytoplasmic reducing
equivalents across the inner membrane of mitochondria. Malate, which
carries the reducing equivalents, is oxidized to oxaloacetate with the
generation of NADH in the matrix. To complete the unidirectional cycle,
oxaloacetate is transported out of the matrix as aspartate. Mai = malate;
OAA = oxaloacetate; a-KG = a-ketoglutarate; Glu = glutamate;
Asp = aspartate.
transferred in the cytoplasm to oxaloacetate, which
is converted to malate. Malate is transported, via the
malate-a:-ketoglutarate translocase, to the mitochondrial
matrix, where it is oxidized to oxaloacetate, accompanied
by the formation of NADH,
which, by respiratory
chain oxidation, produces three molecules of ATP. To
complete the shuttle, oxaloacetate must be transported
from the matrix to the cytoplasm but there is no such
transport system. Instead, oxaloacetate is first converted
to aspartate by aspartate aminotransferase (Chapter 17)
and then transported out of the mitochondria via the
glutamate-aspartate translocase.
14.4 The Mitochondrial Genome
The human mitochondrion contains its own genome; a
circular double-stranded DNA molecule of 16,569 base
pairs. Mitochondrial DNA (mtDNA) is a highly compact
molecule and one of its strands has greater density (heavy-,
H-strand) than the other (light-, L-strand). The only non-
coding region, which consists of about 1 kb of mtDNA,
is known as a
displacement loop
(D-loop). The D-loop
contains the replication origin for H-strand replication
and promoters for transcription from both strands. The
mtDNA consists of 37 genes that encode 13 polypeptides
that are components of the respiratory chain complexes I,
III, IV, and V. Complex I (NADH; ubiquinone oxidore-
ductase) contains seven mtDNA gene products. Complex
III (ubiquinol: cytochrome c oxidoreductase) incorporates
one (cytochrome b); complex IV (cytochrome c oxidore-
ductase) incorporates three; and complex V incorporates
two (Table 14-6). The remainder of the mtDNA genes en-
code 12S and 16S rRNAs and 22 tRNAs.
TABLE 14-6
The Mitochondrial Genes Contributing to the Complexes of
the Mitochondrial Oxidative Phosphorylation Machinery
Encoded
Complex
Total Subunits
by mtDNA
Complex I, NADH:
CoQ reductase
40
7
Complex II,
succinate dehydrogenase
4
0
Complex III,
ubiquinone: cytochrome
c reductase
1 0
1
Complex IV,
cytochrome oxidase
13
3
Complex V, ATP synthase
13
2
Nuclear DNA (nDNA) provides more than 65 oxida-
tive phosphorylation gene products. Overall, oxidative
phosphosphorylation requires at least
1 0 0
gene products;
proteins encoded in nuclear genes are synthesized on cy-
toplasmic ribosomes and imported and assembled within
the mitochondria.
A typical human cell contains many mitochondria with
each mitochondrion having more than one mtDNA. Cyto-
plasmic location and multiple mtDNAs give mitochondria
special characteristics:
• The mtDNA is transmitted through the oocyte
cytoplasm and is maternally inherited.
• The occurrence of a mtDNA mutation creates a mixed
intracellular population of mutant and original
molecules (heteroplasmy). As the heteroplasmic cells
divide during mitosis or meiosis, the mutant and
original mtDNAs are randomly distributed to the
daughter cells. This results in drifting of the
mitochondrial genotype. The replicative segregation
ultimately results in cells with either mutant or normal
mtDNAs (homoplasmy).
• Severe mtDNA defects reduce cellular energy outputs
until they decline below the minimum energy level
(energetic threshold) for normal tissue function. Such
energetic thresholds differ among tissues, with the
brain, heart, muscle, kidney and endocrine organs
being most reliant on mitochondrial energy.
• The mtDNA has a very high mutation rate, some
10-17 times higher than nDNA, which affects both
germ line and somatic tissue mtDNAs. Germ line
mutations result in maternally transmitted diseases or
predispose individuals to late-onset degenerative
