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A NEW HYPOTHESIS 285
How does the hydrogenosome relate to
mitochondria? Like mitochondria, parabasalid
hydrogenosomes are bounded by two membranes
and divide by binary fission independently
of cell division. However, unlike
mitochondria, parabasalid hydrogenosomes
contain no DNA – all the proteins contained
within are synthesized in the cytoplast from
genes harbored in the parabasalid nucleus.
The gene products are then targeted into the
hydrogenosome post-translationally. This targeting
mechanism closely resembles the targeting
of proteins to mitochondria in that an
N-terminal presequence mediates targeting
and is removed within the organelle. Furthermore,
the presequence shares similar properties
to canonical mitochondrial targeting
peptides from mitochondriate organisms. The
question thus arises: is the hydrogenosome a
modified mitochondrion with no DNA? A definitive
answer is not yet available but some strong
lines of evidence speak in the affirmative.
Import of proteins into hydrogenosomes
involves chaperones such as Hsp10, Hsp60 and
Hsp70. Phylogenetic analysis of these proteins
allies them unequivocally with those of eukaryotic
mitochondria. Other components of the
mitochondrial import machinery, namely Tim9,
Tim10, Tim44 and Tom20, are also involved
in hydrogenosome protein targeting. Finally,
eukaryotic mitochondria possess a unique
channel that exchanges ADP from the cytoplasm
for ATP generated in the mitochondrion.
Such a channel does not occur in bacteria (one
wouldn’t expect bacteria to export energy-rich
molecules in exchange for ADP) so it appears to
be an adaptation to the endosymbiotic relationship.
A homologous ADP/ATP exchanger is pre -
sent in hydrogenosomes, suggesting that they
evolved from the same endosymbiotic progenitor
as mitochondria.
If we accept that hydrogenosomes are a modified
form of mitochondria, what happened to
the genome? An attractive hypothesis centers
around the gene content of mitochondrial
genomes. A small number of proteins in the
classical respiratory chain are always encoded
by the mitochondrial DNA. Indeed, in the
malarial mitochondrial genome, the most
stripped down mtDNA known, the three
remaining proteins are all members of the
membrane complexes involved in respiration.
Why these proteins are refractory to transfer of
their genes to the nucleus is uncertain. It may
be that the gene products, which are highly
hydrophobic as membrane proteins, are not
amenable to transport back into the organelle.
Whatever the case, they are invariably encoded
within the genome. However, hydrogenosomes
lack this electron transport chain. The simple
explanation is that the genome was able to disappear
once these proteins were not required
and the organelle was utilized solely for anaerobic
respiration. Thus, parabasalids apparently
have an alternate type of mitochondria, an
anaerobic endosymbiont that has lost its
genome. An interesting question yet to be
resolved is whether the parabasalid mitochondrion
represents a degenerate mitochondrion or
an early offshoot of eukaryotes soon after mitochondrial
acquisition. Various phylogenetic
analyses identify parabasalids as the earliest
diverging eukaryotic lineage. Hydrogenosomes
may thus represent a primitive offshoot of the
endosymbiotic origin of mitochondria.
A NEW HYPOTHESIS
The recent recognition of hydrogenosomes as
a special type of mitochondrion provoked a
rethink of the endosymbiosis theory. The classical
endosymbiotic theory postulates mitochondrial
acquisition being driven by efficiency
of ATP generation. The endosymbiont with its
oxidative phosphorylation pathway introduced
BIOCHEMISTRY AND CELL BIOLOGY: PROTOZOA