22 - The Endosymbiotic Hypothesis (w/ Henry Hsiung!)
22. The Endosymbiotic Hypothesis (w/ Henry Hsiung!)
If I told you that hummingbird flight muscle was one of the richest known sources of mitochondria, could you guess as to what a mitochondrial function is? Today we will discuss the endosymbiotic hypothesis in terms of mitochondria while keeping in mind that the process is equally applicable to chloroplasts. Let’s learn to be scientifically conversational.
During section 4C, Henry mentioned mitochondrial transplantation in the context of removing healthy mitochondria to be put into a cell with unhealthy mitochondria. The technique actually takes a healthy nucleus from the cell with unhealthy mitochondria and puts that nucleus into the recipient cell with healthy mitochondria.
General Learning Concepts
1) What are mitochondria and how are they similar to bacteria?
a. What is the difference between a eukaryote and a prokaryote? Life comes in whatever way we choose to define it, and one way is to examine if an organism is a eukaryote or a prokaryote. In general terms, prokaryotes are what we associate with bacteria while eukaryotes are what we associate with animals and plants.
i. Prokaryotes: Small in size (0.2 – 2 uM) without a nucleus. They do not contain membrane-bound organelles, and divide by binary fission. They have circular DNAs.
ii. Eukaryotes: Larger in size (10 – 100 uM) with a nucleus. They have membrane-bound organelles and divide by both mitosis and meiosis processes. They have linear DNAs.
b. Why would an organism develop membrane-bound organelles? Having organelles allows for organization to do specific functions in their own, enclosed areas. Just as the outer lipid rich plasma membrane acts as a distinctive partition between “inside” the cell and “outside” the cell, organelles act to separate different areas of the cell. By having organelles, cells can concentrate specific proteins (molecular machines) in a certain, smaller area. Cells can also confine molecules that might be harmful in other places of the cell in a specific area (eg. the lysosome, where molecules are digested). 
c. What is a mitochondrion? An organelle responsible for generating metabolic energy in the form of ATP by oxidizing carbohydrates and fatty acids from food. This essentially means that the mitochondria are the organelle responsible for allowing the cell to breathe, freeing most eukaryotes from requiring to use strictly anaerobic respiration for energy (allowing for 15x more ATP than could be provided otherwise). There can be from one to thousands of mitochondria in a cell, depending on energy requirement needs. Mitochondria contain their own set of DNA (circular), encode for some of their own genes, and reproduce independently compared to the cells they are found in by binary fission.
2) What is the endosymbiotic hypothesis?
a. The endosymbiotic hypothesis: First postulated by Lynn Margulis (1938 – 2011, National Medal of Science, National Academy of Sciences) in the 1960’s, the theory was treated with heavy skepticism for a number of years. Endo means within, while endocytosis is a process in which cells engulf something and digest them as food, but endosymbiosis implied a cell was engulfed by not digested. Still, the theory was supported by the similarities between prokaryotes and the mitochondria: similar in size, DNA composition, replication strategy, and some certain proteins. 
b. Origin: Mitochondria are derived from ancient Gram-negative bacteria that had double membranes (four leaflets). Over the time that the larger cell was a symbiont with the smaller cell, the mitochondria lost most of their genes. Some were found within the nucleus of the eukaryotic cell while some were lost entirely (often performing functions that were not essential nor advantageous). Additionally, mitochondria lost their cell wall (as bacteria have cell walls) but this is not novel: mycoplasmas also do not have a cell wall.
c. Further evidence: Mitochondria seem to have a common ancestor to purple-aerobic bacteria: using oxygen in the production of ATP.
3) Resent research examples to show the endosymbiotic hypothesis
a. The Schultz Group: In 2018, Peter Schultz’s research group from Scripps engineered yeast to be endosymbiotic with Escherichia coli. The researchers engineered E. coli to survive the yeast cytosol and to provide ATP to a yeast that was respiration-deficient, and also to have yeast provide thiamin to an E. coli thiamin auxotroph. The system was stable for more than 40 doublings and claims to be able to help provide a system for further endosymbiotic research.
4) Fun Tidbits
a. What are cristae? The double-membraned mitochondrion can be loosely described as a large wrinkled bag packed inside of a smaller, unwrinkled bag. The wrinkles, or folds, are organized into layers called the cristae (singlular: crista). The cristae greatly increase the total surface area of the inner membrane.
b. Chloroplasts: It would be entirely inappropriate to say that this entire process is only true of mitochondria – in fact, the same thing likely happened in plant cells with chloroplasts. In 1883, Amdreas Schimper (a botanist) examined how organelles of plant cells divided and saw that they were quite similar to some bacteria. The chloroplasts in a cell are critical to allow for photosynthesis and are similar to cyanobacteria, bacteria capable of photosynthesis (episode 14, what are bacteria).
c. Mitochondrial transplantation: Recent reports claim being able to scavenge mitochondria from healthy tissue and “transfuse” it into less healthy tissue (like a heart, for instance). This technology is very preliminary. Another strategy is to do mitochondrial transfer, to replace the damaged mitochondria in the mother’s egg with healthy mitochondria from another woman’s donor egg, resulting in a so called “three parent baby”.  
5) Solicited Questions
a. Are mitochondria exclusively inherited by the maternal lineage? Once thought to be absolutely exclusive, recent research makes this out to be the vast majority instead. The paternal mitochondria in C. elegans (episode 16) seems to have an internal self-destruct mechanism activated once a sperm interacts with an egg. Still, recent research has implied that there are “some exceptional cases where paternal mtDNA could be passed to the offspring”. Still, with many responses to this paper, published only last year, the evidence shown seems to be contentious.