The mystery of the origin of mitochondria

We learn about mitochondria (mitochondrion) in the biology courses in middle school, which is an organelle commonly found in eukaryotic cells (there are also very few eukaryotic cells without mitochondria, such as Giardia, trichotillo worms, and other parasites). Because it is the main place for cells to carry out aerobic respiration and the energy manufacturing factory in cells, we also call it the power factory of cells.

Where the mitochondria in eukaryotic cells come from is related to the origin of eukaryotic organisms and is an important topic in the study of biological evolution.

Regarding the origin of mitochondria, there are currently two hypotheses, one is the endosymbiotic origin (endosymbiont hypothesis), and the other is the non-symbiotic origin. These two hypotheses can respectively explain some mitochondrial conditions, so they have always had their own supporters.

The discovery of mitochondria

In 1850, the Swiss-German biologist and anatomist Rudolph Kolliker observed mitochondria in experiments, isolated them, and described their shape and size, but he did not know them at the time function and internal structure, so it is not named.

By the 1880s, with the development of microscopic technology, the magnification of the microscope was greatly increased. German pathologist and histologist Richard Altmann was using a high-power microscope to study the submicroscopic structure of cells. In the structure, a large number of granules are found in energy-demanding cells such as muscle cells. In 1886, he invented the staining method to identify these particles and clearly saw their distribution in the cells under the microscope. He guessed that these particles were not the components of the cells themselves, but bacteria that lived symbiotically with the cells, so he named these particles For the "primary grain" (Bioblast).

In 1897, German biologist Carle Benda (Carle Benda) found that there were a large number of protochores, and the shape was sometimes linear and sometimes granular, so he named the protochondria mitochondria (Mitochondrion). Since then, the scientific community has been using mitochondria as the official name for this particle.

Later, in the study of mitochondrial function, scientists discovered that mitochondria are the place where the tricarboxylic acid cycle, electron transfer, and oxidative phosphorylation occur in cells, thus confirming that mitochondria are the site of energy conversion in eukaryotic cells.

Where do mitochondria come from?

Endosymbiotic origin hypothesis

When Richard Altman observed mitochondria, he proposed that this structure in cells was similar to bacteria and that they were organisms that lived symbiotically in cells and could live independently, but there was no substantial evidence to prove this at the time. In the 1920s, American biologist Ivan E. Wallin proposed the hypothesis that mitochondria originated from endosymbiosis, that is, mitochondria evolved from bacteria that were swallowed by cells, but the scientific community did not recognize it at the time his hypothesis.

In the 1970s, the American biologist Lynn Margulis proposed a relatively complete endosymbiotic theory - primitive eukaryotes swallowed Gram-negative aerobic bacteria in some cases, These aerobic bacteria evolved gradually in the coexistence of primitive eukaryotes, adapted to each other, reached a mutualistic symbiotic relationship, and gradually formed mitochondria. In this symbiotic system, the host (aerobic bacteria) obtains nutrients from the host (primitive eukaryotic cells), and the host can use the energy produced by the host, which increases the competitiveness of the symbiont. This hypothesis has won strong support from the scientific community, and there has been a lot of evidence to prove the scientific nature of the hypothesis.

First, mitochondria have separate genetic material mitochondrial DNA and RNA that is different from that of the eukaryotic nucleus and more similar to that of bacteria.

Second, when cells reproduce themselves, mitochondria also proliferate and distribute at the same time, which is independent and continuous. Its division and proliferation are completed by constriction, similar to bacteria.

Third, mitochondria themselves have an independent and complete protein synthesis system, and most of the characteristics of this synthesis system are similar to those of bacterial protein synthesis systems and are different from eukaryotic protein synthesis systems.

Fourth, mitochondria have an inner membrane and an outer membrane; the inner membrane is similar to the bacterial plasma membrane, and the outer membrane is similar to the eukaryotic inner membrane. Biologists speculate that during the formation of the symbiotic system, when the host phagocytizes the parasitic aerobic bacteria, the inner membrane of the host wraps the host to form the outer membrane of the mitochondria.

Fifth, the hypothesis points out that during the evolution process, most of the original genetic information of aerobic bacteria has been transferred and incorporated into the host cell. Recent studies have found that the genetic information of respiratory bacteria or cyanobacteria exists in the nucleus of eukaryotic cells, confirming the hypothesis.

Sixth, the genetic code of mitochondria is more similar to that of Proteobacteria, and it is believed that mitochondria come from α-Proteobacteria ( α -P rotobacteria).

Seventh, similar symbiotic phenomena still exist in existing living organisms, such as paramecium engulfing cyanobacteria to form symbionts.

There are also some unexplained problems with endosymbiotic origins. The phagocytized aerobic bacterium possesses oxidative metabolic pathways, an ability that apparently gives it an advantage over its engulfed host in the struggle for survival. Then why is this aerobic bacterium at the bottom instead, not only being swallowed as a host, but also transferring its genetic material into the host cell, which does not conform to the law of evolution? Furthermore, the endosymbiotic origin hypothesis cannot explain how the nucleus, the control center of the cell, originated.

Nonsymbiotic origin hypothesis

After the emergence of the hypothesis of endosymbiotic origin, opposition to the nonsymbiotic origin hypothesis also emerged. The non-symbiotic hypothesis conjectures that eukaryotic cells originate from an aerobic bacterium. During the evolution of this bacterium, some cell membranes with respiration function gradually invaginated to wrap part of the genetic material, forming an independent genetic material and Respiratory function and membrane structure of mitochondria.

There is also some evidence for the nonsymbiotic origin hypothesis. For example, some primitive aerobic bacteria now have a pseudo-mitochondrion structure, which is formed by invagination of the plasma membrane and has a respiratory function; the structure with a respiratory function in prokaryotic cells can be regarded as the embryonic form of today's mitochondria, so it is speculated that Mitochondria evolved rather than phagocytic symbiosis; eukaryotic nuclear membranes and mitochondrial membranes have continuity, indicating that mitochondria may originate from the invagination of the cell's own inner membrane system, rather than from symbiotic bacteria.

Controversies in the endosymbiotic origin hypothesis

Although the endosymbiotic origin hypothesis has some unexplained problems, it provides more evidence than non-endosymbiotic origin, so it has become the most mainstream theory of mitochondrial origin.

Among the endosymbiotic origin hypotheses, there are two schools of thought based on the timing of mitochondrial endosymbiosis.

One school of hypothesis is called the late mitochondrial model ("Mito-late" models), they believe that the host has passed through different pathways before engulfing the aerobic α-proteobacteria (now there is a lot of evidence to prove that mitochondria evolved from it) The nucleus has been formed, and it has the characteristics of eukaryotic cells (nucleus, dynamic cytoskeleton, endomembrane system), and has a primitive phagocytic function. That is, the mitochondrial progenitor (α-proteobacteria) entered the host (primitive eukaryotic cells) later.

The hypothesis put forward by another school is called the early mitochondrial model (“Mito-early” models). They believe that the host (prokaryotic cell) first symbiotically formed a prokaryotic cell with mitochondria with aerobic α-proteobacteria. After having this power plant After that, eukaryotic features such as the nucleus and inner membrane system evolved.

The debate between the two factions focuses on the time point when the mitochondrial ancestor (α-proteobacteria) enters the host. Why is this time point so important?

Because this mitochondrial ancestor entered the eukaryotic cell ancestor, how it entered is an extremely important point of discussion. Some scientists believe that it enters through phagocytosis, while others believe that cells have phagocytosis after they have mitochondria. So, the question turned to phagocytosis.

Phagocytosis is the action of certain cells to engulf microorganisms or small objects in a deformed motion. This seemingly simple process actually requires a lot of energy, as well as the dynamic cytoskeleton and membrane transport capacity of cells.

If it takes a lot of energy for a cell to phagocytose bacteria, it simply would not be able to phagocytose the mitochondrial ancestors without the energy factories of the mitochondria to power them. However, at this time, the ancestors of mitochondria have not been swallowed, so how can mitochondria become the energy factory of cells? In this way, it's like entering a time vortex. What came first, the chicken or the egg? That is, do mitochondria come first, or does phagocytosis come first?

If there was phagocytosis first, the ancestors of eukaryotic cells had already evolved to a certain extent when they phagocytized the ancestors of mitochondria. The arrival of mitochondria was just the icing on the cake in the evolution of eukaryotic cells. This is the late mitochondrial hypothesis. However, if there were mitochondria first, mitochondria provided a lot of energy for the ancestors of eukaryotic cells, because of this energy factory, the ancestors of eukaryotic cells were promoted by it to evolve and formed later eukaryotic cells, then the evolution of mitochondria for eukaryotic cells is This is the early mitochondrial hypothesis.

The dispute between the early and late models of mitochondrial endosymbiosis has not yet been settled. The two schools of thought have their own evidence and put forward many hypotheses.

For example, in 1998, Bill Martin and Miklos Muller put forward the "Hydrogen Hypothesis" - an archaea that need hydrogen to produce methane as a host and a Hydrogen-producing α-proteobacteria fuse, and the two depend on each other to form a stable symbiotic relationship. This model shows that after the endosymbiosis of the mitochondrial ancestors, the generation of eukaryotes was triggered by the possession of mitochondria that produce a large amount of energy, indicating that there are mitochondria first before eukaryotic cells and phagocytosis. This hypothesis is the best-known early model of mitochondria. But scientists who have questioned the hypothesis argue that the methane-producing process in this model is complex and requires a large number of coenzymes that are not found in eukaryotes today.

For the late mitochondrial hypothesis, Anthony M. Poole and Nadja Neumann in 2011, Joran Martijn and Thijs JG Ettema ) the phagocytosing archaeon model (PhAT) proposed in 2013; the symbiosis hypothesis proposed by Lopez Garcia et al. The endosymbiotic model was proposed by Pittis Alexandros et al. in 2016. In these models, they all believed that mitochondria formed late, especially the phagocytic archaea model, and believed that the phagocytic mechanism was a prerequisite for the fusion of mitochondrial ancestors and eukaryotic cell ancestors.

Overall, the early mitochondrial hypothesis is more prevalent today.

Looking for new evidence

In February this year, a paper published in Molecular Biology and Evolution added another piece of evidence to the late mitochondrial hypothesis through experiments.

In the paper, the team of evolutionary microbiologist Lionel Guy at Uppsala University in Sweden sequenced bacteria of the order Legionellales, which are intracellular parasites. Bacteria can grow inside eukaryotic cells. By analyzing the genomes of 35 Legionella species, they constructed the evolutionary history of Legionella and its relationship to early hosts. Using the biomarker Okenone to trace back, Guy's team concluded that the first host-adapted Legionella ancestor existed 1.89 billion years ago. In other words, at the time point of 1.89 billion years, the ancestors of Legionella had already infected the ancestors of eukaryotes. This infection was carried out through phagocytosis, which can also prove from the side that there is a phagocytosis mechanism at this time. However, many current studies believe that cells containing mitochondria first appeared nearly 1.5 billion years ago, which is later than the time when the phagocytic mechanism existed. In this way, the emergence of mitochondria was after the phagocytosis of eukaryotic ancestors-first phagocytosis, and then mitochondria, providing evidence for the late mitochondrial hypothesis.

However, some scientists have proved that the endosymbiosis of mitochondria was very early, which is believed to be between 1.21 billion and 2.053 billion years, and even more believed to be between 2 billion and 2.4 billion years. If the time of endosymbiosis in mitochondria is so early, then using Professor Guy's evidence, they cannot prove that phagocytosis predates the formation of mitochondria.

The early, and late debate on mitochondrial endosymbiosis remains inconclusive. There are many intricate details about the origin of the mitochondria that remain to be studied and explained, but whatever the conclusions, the facts demonstrate that the combination of eukaryotic and mitochondrial progenitors produced a huge competitive advantage for survival. This strong competitiveness and continuous evolution have formed our colorful world today, including us in this world.