Oxidative Phosphorylation in Eukaryotes Takes Place in Mitochondria

II. Transducing and Storing Energy
18. Oxidative Phosphorylation
Mitochondria, Stained Green, Form a Network Inside a Fibroblast Cell (Left). Mitochondria oxidize carbon fuels to
form cellular energy. This transformation requires electron transfer through several large protein complexes (above),
some of which pump protons, forming a proton gradient that powers the synthesis of ATP. [(Left) Courtesy of Michael
P. Yaffee, Dept. of Biology, University of California at San Diego.]
II. Transducing and Storing Energy
18. Oxidative Phosphorylation
18.1. Oxidative Phosphorylation in Eukaryotes Takes Place in Mitochondria
Mitochondria are oval-shaped organelles, typically about 2 µm in length and 0.5 µm in diameter, about the size of a
bacterium. Eugene Kennedy and Albert Lehninger discovered a half-century ago that mitochondria contain the
respiratory assembly, the enzymes of the citric acid cycle, and the enzymes of fatty acid oxidation.
18.1.1. Mitochondria Are Bounded by a Double Membrane
Electron microscopic studies by George Palade and Fritjof Sjöstrand revealed that mitochondria have two membrane
systems: an outer membrane and an extensive, highly folded inner membrane. The inner membrane is folded into a
series of internal ridges called cristae. Hence, there are two compartments in mitochondria: (1) the intermembrane space
between the outer and the inner membranes and (2) the matrix, which is bounded by the inner membrane (Figure 18.3).
Oxidative phosphorylation takes place in the inner mitochondrial membrane, in contrast with most of the reactions of the
citric acid cycle and fatty acid oxidation, which take place in the matrix.
The outer membrane is quite permeable to most small molecules and ions because it contains many copies of
mitochondrial porin, a 30 35 kd poreforming protein also known as VDAC, for voltage-dependent anion channel.
VDAC plays a role in the regulated flux of metabolites usually anionic species such as phosphate, chloride, organic
anions, and the adenine nucleotides across the outer membrane. VDAC appears to form an open β -barrel structure
similar to that of the bacterial porins (Section 12.5.2), although mitochondrial porins and bacterial porins may have
evolved independently. Some cytoplasmic kinases bind to VDAC, thereby obtaining preferential access to the exported
ATP. In contrast, the inner membrane is intrinsically impermeable to nearly all ions and polar molecules. A large family
of transporters shuttles metabolites such as ATP, pyruvate, and citrate across the inner mitochondrial membrane. The
two faces of this membrane will be referred to as the matrix side and the cytosolic side (the latter because it is freely
accessible to most small molecules in the cytosol). They are also called the N and P sides, respectively, because the
membrane potential is negative on the matrix side and positive on the cytosolic side.
In prokaryotes, the electron-driven proton pumps and ATP-synthesizing complex are located in the cytoplasmic
membrane, the inner of two membranes. The outer membrane of bacteria, like that of mitochondria, is permeable to most
small metabolites because of the presence of porins.
18.1.2. Mitochondria Are the Result of an Endosymbiotic Event
Mitochondria are semiautonomous organelles that live in an endosymbiotic relation with the host cell. These
organelles contain their own DNA, which encodes a variety of different proteins and RNAs. The genomes of
mitochondrial range broadly in size across species. The mitochondrial genome of the protist Plasmodium falciparum
consists of fewer than 6000 base pairs (6 kbp), whereas those of some land plants comprise more than 200 kbp (Figure
18.4). Human mitochondrial DNA comprises 16,569 bp and encodes 13 respiratory-chain proteins as well as the small
and large ribosomal RNAs and enough tRNAs to translate all codons. However, mitochondria also contain many
proteins encoded by nuclear DNA. Cells that contain mitochondria depend on these organelles for oxidative
phosphorylation, and the mitochondria in turn depend on the cell for their very existence. How did this intimate
symbiotic relation come to exist?
An endosymbiotic event is thought to have occurred whereby a freeliving organism capable of oxidative phosphorylation
was engulfed by another cell. The double membrane, circular DNA (with some exceptions), and mitochondrial-specific
transcription and translation machinery all point to this conclusion. Thanks to the rapid accumulation of sequence data
for mitochondrial and bacterial genomes, it is now possible to speculate on the origin of the "original" mitochondrion
with some authority. The most mitochondrial-like bacterial genome is that of Rickettsia prowazekii, the cause of louseborne typhus. The genome for this organism is more than 1 million base pairs in size and contains 834 protein-encoding
genes. Sequence data suggest that all extant mitochondria are derived from an ancestor of R. prowazekii as the result of a
single endosymbiotic event.
The evidence that modern mitochondria result from a single event comes from examination of the most bacteria-like
mitochondrial genome, that of the protozoan Reclinomonas americana. Its genome contains 97 genes, of which 62
specify proteins that include all of the protein-coding genes found in all of the sequenced mitochondrial genomes (Figure
18.5). Yet, this genome encodes less than 2% of the protein-coding genes in the bacterium E. coli. It seems unlikely that
mitochondrial genomes resulting from several endosymbiotic events could have been independently reduced to the same
set of genes found in R. americana.
Note that transient engulfment of prokaryotic cells by larger cells is not uncommon in the microbial world. In regard to
mitochondria, such a transient relation became permanent as the bacterial cell lost DNA, making it incapable of
independent living, and the host cell became dependent on the ATP generated by its tenant.
II. Transducing and Storing Energy
18. Oxidative Phosphorylation
18.1. Oxidative Phosphorylation in Eukaryotes Takes Place in Mitochondria
Figure 18.3. Diagram of a Mitochondrion. [After Biology of the Cell by Stephen L. Wolfe. © 1972 by Wadsworth
Publishing Company, Inc., Belmost, California 94002. Adapted by permission of the publisher.]
II. Transducing and Storing Energy
18. Oxidative Phosphorylation
18.1. Oxidative Phosphorylation in Eukaryotes Takes Place in Mitochondria
Figure 18.4. Sizes of Mitochondrial Genomes. The sizes of three mitochondrial genomes compared with the genome of
Rickettsia, a relative of the the presumed ancestor of all mitochondria. For genomes of more than 60 kbp, the DNA
coding region for genes with known function is shown in red.