Their name is derived from Greek mitos,
"thread", and chondros, "grain" or "seed".
In some cells mitochondria are long, almost filamentous, but
in most others they are elliptical or spherical. In each liver
cell of the rat there are perhaps 1000 mitochondria. They have
a diameter of about 1 micrometer, close to the size of bacterial cells.
Some types of eukaryotic cells contain only a few very large
mitochondria (e.g., sperm cells or yeast cells), whereas others
contain many thousands (e.g., egg cells). Each mitochondrion
has two membrane systems. The outer membrane is smooth, surrounding
the mitochondrion completely. The inner membrane has infoldings
called cristae. The inner compartment of mitochondria is filled
with gel-like matrix.
Mitochondria generally contain several copies of small circular
DNA as well as RNA and ribosomes. Mitochondrial DNA codes for
subunits of enzyme complexes involved in oxidative phosphorylation.
One may well ask why mitochondria contain DNA. This question
has led to the interesting concept that mitochondria originally
arose during biological evolution by the invasion of cytoplasm
of large anaerobic prokaryotic cells by smaller prokaryotes capable
of using molecular oxygen to oxidize their nutrients within the
host cells.
The mitochondria are the power plants of the cells. They contain
many enzymes that together catalyze the oxidation of organic cell
nutrients by molecular oxygen to yield carbon dioxide and water.
Some of these enzymes are located in the matrix and some in the
inner membrane. Much chemical energy is released during these
oxidations, which is used to generate ATP, the major energy-carrying
molecule of cells.
In mammalian mitochondria,
this system is composed of five enzyme complexes. Those are NADH-quinone
oxidoreductase (complex I), succinate-quinone oxidoreductase (complex
II), Quinol-cytochrome c oxidoreductase (complex III or bc1 complex),
Cytochrome c oxidase (complex IV), and ATP synthase (complex V).
This enzyme complex is one of three energy-transducing
complexes that constitute the respiratory chain in mammalian mitochondria.
This NADH-Q oxidoreductase is the point of entry for majority
of electrons that traverse the respiratory chain eventually resulting
in the reduction of oxygen to water. In 1961, the mitochondrial
H+-translocating NADH-Q oxidoreductase (complex I)
was first isolated from bovine heart by Hatefi and coworkers.
This enzyme complex is composed of at least 46 dissimilar subunits.
As far as our present knowledge is concerned, complex I has the
most intricate structure of the membrane-bound enzyme complex.
Research on complex
I has recently taken on greater significance since the finding
that many human mitochondrial diseases involve structural and
functional defects at the level of this enzyme complex. Examples
include a variety of neuromuscular diseases, including myoclonic
epilepsy and ragged red fibers (MERRF); mitochondrial encephalomyopathy,
lactic acidosis and stroke-like episodes (MELAS); Chronic External
Ophthalmoplegia Plus (CEOP); Kearns-Sayre syndrome (KSS). Many
cases of Leber's hereditary optic neuropathy (LHON), appear to
be associated with a defect in complex I. The defect identified
in many cases is a single nucleotide change in the mitochondrial
DNA converting the 340th amino acid of the ND4 subunit of complex
I from an arginine to a histidine. In addition to these documented
cases, the compound, 1-methyl-4-phenylpyridium, an inhibitor of
complex I, produces idiopathic Parkinsonism in rats and human,
which suggests a link between Parkinson's disease and function
of mitochondrial complex I.
In spite of
its structural complexity, the results of a strategy designed
to investigate complex I directly have been reported. It is clear
that this approach has met with limited success. Another approach
is to find a simpler system in which the elucidation of the structural
and functional relationships within complex I will also be simpler.
Because bacterial respiratory enzyme complexes are known to be
generally simpler in structure than their mitochondrial counterparts
while retaining similarity to their mitochondrial counterparts
in terms of electron carriers, we screened various bacterial species
in terms of their NADH-Q oxidoreductases. In the course of this
research, the various bacterial NADH-q oxidoreductases were found
to fall into one of the following 3 categories: NDH-2, Na+-NDH,
or NDH-1. Those enzyme complexes lacking an energy-coupling site
are known as NDH-2 (NADH dehydrogenase 2). Those enzymes which
bear an energy-coupling site are designated Na+-NDH,
if they pump sodium ions, or NDH-1 (NADH dehydrogenase 1) if they
function as H+ pumps.
Paracoccus
denitrificans is a Gram-negative soil bacterium and has
been called "a free-living mitochondrion" because of
similarity in electron transfer components, similarity of 16S
rRNA sequence between this bacterium and mitochondria, and similarities
of amino acid sequences of various enzymes. Aerobically grown
Paracoccus expresses a mammalian mitochondrial type respiratory
chain which contains NDH-1. Therefore, the Paracoccus
NDH-1 is a useful model for study of mitochondrial complex I.
Thermus thermophilus,
which was isolated from a hot spring in Japan, is an extremely
thermophilic, obligatory aerobic, Gram-negative, and chemoheterotrophilic
bacterium. The bacterium is capable of growing in the temperature
range from 45C to 85C with optimum growth temperature of 70C.
Its respiratory chain contains NDH-1. The thermostability of
the NDH-1 is expected to provide a great advantage for structural
studies of the NDH-1.