The Origin of Mitochondria

Mitochondria arose through a fateful endosymbiosis more than 1.45 billion years ago.
Many mitochondria make ATP without the help of oxygen.

What variety is there in mitochondria? Mitochondria occur in various forms across

various eukaryotic groups, yet considerations on the origin of mitochondria sometimes
neglect this understanding. Four main mitochondrial types can be distinguished on the
basis of functional criteria concerning how or whether ATP is produced. These
functional types do not correspond to natural groups, because they occur in an
interleaved manner across the tree of eukaryotic life. Instead they correspond to
ecological specializations.

Mitochondria: A Ubiquitous and Diverse Family of Organelles

The mitochondria typical of mammalian cells respire O 2 during the process of pyruvate
breakdown and ATP synthesis, generating water and carbon dioxide as end products.
The Krebs cycle and the electron transport chain in the inner mitochondrial membrane
enable the cell to generate about 36 moles (mol) of ATP per mole of glucose, with the
help of O2–respiring mitochondria. Such typical mitochondria also occur in plants and
various groups of unicellular eukaryotes (protists) that, like mammals, are dependent on
oxygen and specialized to life in oxic environments.
In contrast, the mitochondria of many invertebrates (worms like Fasciola hepatica and
mollusks like Mytilus edulis being well–studied cases) do not use O 2 as the terminal
acceptor during prolonged phases of the life cycle. These mitochondria allow the
anaerobically growing cell to glean about 5 mol of ATP per mole of glucose, as opposed
to about 36 with O2. The typical excreted end products are carbon dioxide, acetate,
propionate, and succinate, which are generated mostly through the rearrangement of
Krebs cycle reactions and the help of the mitochondrial electron transport chain. These
organelles are commonly called anaerobic mitochondria.
Mitochondria of yet another kind yield even less ATP per molecule of glucose. These
are mitochondria of several distantly related unicellular eukaryotes (protists) that lack an
electron transport chain altogether. They synthesize ATP from pyruvate breakdown via
simple fermentations that typically involve the production of molecular hydrogen as a
major metabolic end product. These mitochondria are called hydrogenosomes and
allow the cell to gain about 4 mol of ATP per mole of glucose. Hydrogenosomes were
discovered in 1973 in trichomonads, a group of unicellular eukaryotes. They were later
found in chytridiomycete fungi that inhabit the rumen of cattle, as well as some ciliates,
and they continue to be found in other groups. The enzymes of hydrogenosomes are
not unique to these anaerobes. They are found also in the mitochondria, the cytosol, or
even the plastids of other eukaryotes (Figure 1).
A fourth category of eukaryotes possesses small, inconspicuous mitochondria that are
not involved in ATP synthesis at all. These eukaryotes synthesize their ATP in the
cytosol with the help of enzymes that are otherwise typically found in hydrogenosomes.
They obtain 2-4 mol of ATP per mole of glucose. Their typical end products are carbon
dioxide, acetate, and ethanol, and their mitochondria are called mitosomes. Mitosomes
were discovered in the human intestinal parasite Entamoeba histolytica in 1999, and
were subsequently found in many additional eukaryotes, including Giardia lambliain
2003.
Knowledge about these different forms of mitochondria comes from decades of
biochemical and physiological investigations of eukaryotic anaerobes, many of which
are important pathogens or parasites of humans and livestock. Well into the 1990s it
was widely thought that several anaerobic eukaryotes, such as Giardia lamblia, lack
mitochondria altogether and had never possessed them in the evolutionary past. Newer
work, however, has shown that mitochondria are just as defining and ubiquitous among
eukaryotes as is the nucleus itself. That realization has had considerable impact on
current views about the origin of mitochondria.

The Endosymbiotic Origin of Mitochondria

There are currently two main, competing theories about the origin of mitochondria. They
differ with regard to their assumptions concerning the nature of the host, the
physiological capabilities of the mitochondrial endosymbiont, and the kinds of ecological
interactions that led to physical association of the two partners at the onset
of symbiosis.
The traditional view posits that the host that acquired the mitochondrion was an
anaerobic nucleus-bearing cell, a full-fledged eukaryote that was able to engulf the
mitochondrion actively via phagocytosis (Figure 2). This view is linked to the ideas that
the mitochondrial endosymbiont was an obligateaerobe, perhaps similar in physiology
and lifestyle to modern Rickettsiaspecies; and that the initial benefit of the symbiosis
might have been the endosymbiont's ability to detoxify oxygen for the anaerobe host.
Because this theory presumes the host to have been a eukaryote already, it does not
directly account for the ubiquity of mitochondria. That is, it entails a corollary assumption
(an add–on to the theory that brings it into agreement with available observations) that
all descendants of the initial host lineage, except the one that acquired mitochondria,
went extinct. The oxygen detoxification aspect is problematic, because the forms of
oxygen that are toxic to anaerobes are reactive oxygen species (ROS) like the
superoxide radical, O2-. In eukaryotes, ROS are produced in mitochondria because of
the interaction of O2 with the mitochondrial electron transport chain. In that sense,
mitochondria do not solve the ROS problem but rather create it; hence, protection from
O2 is an unlikely symbiotic benefit. This traditional view also does not directly account
for anaerobic mitochondria or hydrogenosomes, and additional corollaries must be
tacked on to explain why anaerobically functioning mitochondria are found in so many
different lineages and how they arose from oxygen-dependent forebears.

An alternative theory posits that the host that acquired the mitochondrion was
a prokaryote, an archaebacterium outright. This view is linked to the idea that the
ancestral mitochondrion was a metabolically versatile, facultativeanaerobe (able to live
with or without oxygen), perhaps similar in physiology and lifestyle to modern
Rhodobacteriales. The initial benefit of the symbiosis could have been the production of
H2 by the endosymbiont as a source of energy and electrons for the archaebacterial
host, which is posited to have been H 2 dependent. This kind of physiological interaction
(H2 transfer or anaerobic syntrophy) is commonly observed in modern microbial
communities. The mechanism by which the endosymbiont came to reside within the
host is unspecified in this view, but in some known examples in nature prokaryotes live
as endosymbionts within other prokaryotes. In this view, various aerobic and anaerobic
forms of mitochondria are seen as independent, lineage-specific ecological
specializations, all stemming from a facultatively anaerobic ancestral state. Because it
posits that eukaryotes evolved from the mitochondrial endosymbiosis in a prokaryotic
host, this theory directly accounts for the ubiquity of mitochondria among all eukaryotic
lineages.
Eukaryotes are genetic chimeras. They possess genes that they inherited vertically from
their archaebacterially related host. Genes for cytosolic ribosomes in eukaryotes, for
example, reflect that origin. But eukaryotes also possess genes that they inherited
vertically from the endosymbiont - for example, mitochondrially encoded genes for
mitochondrial ribosomes. But even the largest mitochondrial genomes possess only
about sixty protein-coding genes, while typical mitochondria harbor up to a thousand
proteins or more that are encoded in the nucleus. During the course of mitochondrial
genesis, many genes were transferred from the genome of the mitochondrial
endosymbiont to the genome of the host. This kind of endosymbiotic gene transfer is
nothing unusual; endosymbiosis very often entails gene transfers from the
endosymbiont to the host. It happened during the origin of plastids too, and it is still
ongoing in our own genome: Mitochondrial DNA constantly escapes from the organelle
and becomes integrated as copies into nuclear DNA. The vast majority of mitochondrial
proteins are encoded by nuclear genes, and many of these are endosymbiotic
acquisitions from the mitochondrial ancestor.

When and How Often Did Mitochondria Arise?

The oldest undisputedly eukaryotic microfossils go back 1.45 billion years in the fossil
record. Given the coincidence of mitochondria with the eukaryotic state, this can also be
seen as a minimum age for mitochondria and a rough best-guess starting date for
eukaryotic evolution. According to newer geochemical views, this date of origin
corresponds to a protracted phase in Earth history when the oceans were mostly anoxic
— from 1.8 billion years ago until about 580 million years ago — because of the
workings of marine, H2S-producing bacteria. Eukaryotes thus arose and diversified in
an environment where anoxia was commonplace. Accordingly it is hardly surprising that
many independent eukaryotic lineages have preserved anaerobic energy-producing
pathways in their mitochondria (Figure 3).
Like eukaryotes themselves, mitochondria appear to have arisen only once in all of
evolution. The best evidence for the single origin of mitochondria comes from a
conserved set of clearly homologous and commonly inherited genes preserved in
the mitochondrial DNA across all known eukaryotic groups. In the case of
hydrogenosomes (which usually lack DNA) and mitosomes (which so far always lack
DNA), the strongest evidence for their common ancestry with mitochondria is twofold.
First, aspects and components of the mitochondrial protein import process are
conserved in hydrogenosomes and mitosomes, arguing strongly for common ancestry
with mitochondria. Second, all known lineages of eukaryotes that possess
hydrogenosomes or mitosomes branch as sisters to mitochondrion-bearing lineages.

Summary

Mitochondria arose once in evolution, and their origin entailed an endosymbiosis

accompanied by gene transfers from the endosymbiont to the host. Anaerobic
mitochondria pose a puzzle for traditional views on mitochondrial origins but fit nicely in
newer theories on mitochondrial evolution that were formulated specifically to take the
common ancestry of mitochondria and hydrogenosomes into account. The presence of
mitochondria in the eukaryote common ancestor continues to change the way we look
at eukaryote origins, with endosymbiosis playing a more central role in considerations
on the matter now than it did twenty years ago. The integral part that mitochondria play
in many aspects of eukaryote biology might well reflect their role in the origin of
eukaryotes themselves.