trans

MITOCHONDRIAL METABOLISM 281
Cofactors of this reduction, such as NAD ,
temporarily hold the electrons from the oxidized
carbon–carbon bonds prior to transfer
into the electron-transport chain of oxidative
phosphorylation. Further transfer of the electrons
along the chain drives proton pumps that
establish an electrochemical gradient across
the inner and outer mitochondrial membranes.
This gradient is used to rotate the ATPase, and
the rotation energy is converted to chemical
energy by phosphorylation of ADP to ATP.
Ultimately the electrons are transferred to
O 2 to produce H 2 O. Do parasite mitochondria
perform similar functions? Sometimes.
Depending on the parasite in question, quite
a range of mitochondrial functions is evident.
In kinetoplastid parasites, for instance, the
mitochondrion apparently performs similar
functions to homologous organelles in other
eukaryotes. In other parasites, though, the role
of the mitochondrion is far from typical. Indeed,
in many parasites the mitochondrion performs
bizarre reactions not commonly seen elsewhere
in eukaryotes. These reactions are probably
adaptations to the extraordinary environmental
conditions in which these parasites live.
Additionally, these atypical metabolisms of
parasite mitochondria are often relatively low
in efficiency. Such low efficiency may reflect
the fact that the success of the parasite may
not require maximal efficiency in utilizing
energy resources, which after all are being
acquired from the host.
The atypical metabolisms of parasite mitochondria
have proven to be useful targets for
several drugs. For instance, mitochondria of
malaria parasites are the target of the antimalarial
drug atovaquone. The exact role
of malaria parasite mitochondria is unclear.
The mitochondrial genome is the smallest
known and encodes only five genes: two rRNAs
and three proteins (CoxI, CoxII and Cytb). The
rRNAs are highly fragmented, but careful
reconstruction of the fragments suggests they
have a viable secondary structure, which indicates
that a translation system for expression is
probably operative. All translation components
other than rRNAs are presumably imported.
Structurally the malaria parasite mitochondrion
is also unusual. In erythrocyte stages
virtually no cristae are present, and only in
gametocytes does the organelle resemble other
eukaryotic mitochondria, with so-called tubular
cristae. Little is known about mitochondrial
metabolism in P. falciparum. The parasite is
considered to be a homolactic fermenter.
Recently, it has been demonstrated that the
P. berghei mitochondrion is capable of oxidative
phosphorylation, but that the proton gradient
is uncoupled. The malaria parasite mitochondria
contain ubiquinones, the electron carrier
molecules embedded in the inner mitochondrial
membrane, and the anti-malarial atovaquone
is a ubiquinone analog. Atovaquone
apparently inhibits the cytochrome bc(1) complex
of the cytochrome pathway. It is effective
against malaria, toxoplasmosis and other parasites
such as Pneumocystis carinii pneumonia.
Utility of atovaquone as an anti-malarial is limited
due to resistance arising via a mutation
to the catalytic domain of the bc(1)complex
(Chapters 16, 17).
Mitochondria of kinetoplastid parasites
(e.g. trypanosomes and Leishmania) are also
unusual. The name kinetoplastid derives from
the unique mitochondria of these parasites.
The mitochondrion, which stains heavily due
to presence of extraordinary amounts of DNA,
typically lies just posterior to the flagellar bases
and was initially thought to have a special role
in motility, hence kinetoplastid (motility body).
The large quantity of DNA reflects a special
type of genome organization in kinetoplastids.
Kinetoplastid mitochondria depart from the
so-called ‘central dogma of molecular biology’,
which dictates that information is passed from
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA