If the inner mitochondrial
membrane is impermeable to NAD
and NADH, it is somewhat of a puzzle how the NADH produced in the
cytoplasm during glycolysis ever gets to the site of the respiratory
chain where it can be reoxidized and its energy used to make ATP.
NADH from glycolysis never enters the mitochondrion at all, but
passes its free energy to a shuttle molecule that can penetrate
the membrane. What is not clear is the identity of the shuttle.
In the most likely mechanism, the shuttle molecule is reduced by
NADH outside the mitochondrion, diffuses inside, and then is reoxidized
in the process of reducing FAD to FADH.
Since the respiratory chain makes only two ATP per FADH,
this represents a loss or a "toll fee" of one of the three ATP equivalents
for every NADH made by glycolysis outside the mitochondrion. If
this is the actual mechanism, the net production of ATP per molecule
of glucose would be reduced from 38 to 36, but we will continue
to use the 38 ATP figure for simplicity. This uncertainty illustrates
both the shallowness of our present knowledge about some aspects
of cell chemistry, and the remarkable extent to which the mitochondrion
is really "outside" the rest of the cell.
Mitochondria also have
their own limited genetic apparatus: DNA, polymerase and transcriptase
enzymes to make more DNA and to copy the information off as messenger
RNA, and ribosomes for protein synthesis. The DNA of mitochondria
is small and circular, like that found in bacteria. The polymerases
are different from those found in a cell nucleus, and the ribosomes
resemble bacterial ribosomes rather than those of cell cytoplasm.
The mitochondrion is capable of transcribing information to messenger
RNA and synthesizing proteins.
A few years ago it was believed that the only proteins coded in
mitochondrial DNA were some of the structural proteins of the inner
membrane and cristae. Recently other proteins have been found, including
some of the polypeptides of enzymes involved in the respiratory
chain. However, most of these enzymes, and all other enzymes of
the citric acid cycle and ATP synthesis, are synthesized from nuclear
DNA in the cytoplasm, and diffuse into the mitochondria afterwards.