Mitochondria: more essential than Midichlorians?

By Reed Stubbendieck (@bactereedia)

Midichlorians are a microscopic lifeform that resides within all living cells… And we are symbionts with them… Lifeforms living together for a mutual advantage. Without the midichlorians, life could not exist, and we would have no knowledge of the Force.

Qui-Gon Jinn, Star Wars Episode 1: The Phantom Menace

Note: this post contains a minor spoiler for Star Wars: Episode VIII – The Last Jedi

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Image Credit: Wookieepedia

In one conversation between Jedi Master Qui-Gon Jinn and Anakin Skywalker, the origin of the Force shifted from the mystical to the microbiological. And while I love all things microbiology, I can’t say that even a ten-year old Reed appreciated the introduction of midichlorians into the Star Wars canon (though let’s be fair, not many people did).

Qui-Gon Jinn says that life cannot exist without midichlorians and the Force is conducted through the midichlorians and refers to the midichlorians as microscopic lifeforms that live inside our cells. It’s well documented that Star Wars director George Lucas derived inspiration for midichlorians from an organelle that exists within most of our own cells called the mitochondria. 

Similarly to midichlorians, all human life is dependent upon mitochondria. However, while midichlorians connect living things to the Force, our mitochondria connect us to an even more powerful force: aerobic metabolism!

In today’s post, we will explore what would happen if a human being was suddenly cut off from the force of aerobic metabolism (much like how Luke cut himself off from the Force in The Last Jedi). More specifically, we will determine how long a human can survive if they were to suddenly lose all of their mitochondria.

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Transmission electron micrograph of a mitochondrion. Image credit: G. Angus McQuibban

Before we begin, I will briefly describe the function of our mitochondria (pictured above), which are (in)famous for being “the powerhouse of the cell”. That is, most of our energy generation occurs due to biochemical reactions that take place within the mitochondria.

Learning about metabolism is one of the banes of introductory biochemistry courses, but for our purposes, we can represent the many enzyme-catalyzed reactions, substrates, cofactors into a single equation, where C6H12O6 is glucose (a sugar) that we consume and adenosine triphosphate (ATP) is the energy currency of our cells:

eq1

This process, which is called oxidative phosphorylation, absolutely requires our mitochondria to occur. Without mitochondria, our cells can metabolize glucose in an oxygen-independent process called anaerobic glycolysis. However, anaerobic glycolysis is much less efficient than oxidative phosphorylation and causes a buildup of lactic acid. Under conditions of oxygen deprivation (e.g., asphyxiation), our brains rapidly suffer damage due to a combination of lack of energy and acid buildup in brain tissue.

Similar to my first post, I will use back-of-the-envelope calculations to estimate how long a human will survive without their mitochondria. I will make the following two assumptions:

1) The first organ to suffer irreparable damage from complete loss of mitochondria is the brain.

2) Death will occur due to lack of energy, in the form of ATP molecules.

To determine how many long it would take for our brains to deplete their total ATP, we need to determine how much ATP our brains contain and the rate of ATP consumption. First, we will calculate the amount of ATP in our brains. A rat neuron contains 2.6 mM ATP, an average human cell has a volume of 4000 µm3, and the brain contains ~240 billion cells. Using these numbers we can estimate the ATP content in a human brain:

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This number corresponds to ~1.4 grams of ATP contained in our brains. For comparison, a paperclip has a mass of ~1 gram.

Next, we need to determine how much ATP our brains generate. Under normal conditions, over the course of a single day, we produce ~60 kg of ATP! Using this rate, we can calculate how much ATP our bodies generate per second:

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But, recall that if we suddenly lose all of our mitochondria, then we can only generate ATP from anaerobic glycolysis, which only yields 2 molecules of ATP for every molecule of glucose, which is 18× less efficient than oxidative phosphorylation:

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Our brains use roughly 20-25% of the total oxygen that we consume, so one-quarter of the ATP that we produce occurs in our brains. With this, we can calculate how much ATP generation occurs per second in the brain:

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Finally, we need to calculate how much ATP our brains use. The human brain consumes 80 µM of ATP per second and averages 1.5 liters in volume. Using simple multiplication, we calculate:

eq6

Now we have all the numbers to determine how long it takes for our brains to deplete their ATP after losing all our mitochondria. We know our brains contains 2500 µmol of ATP,  they produces 20 µmol of ATP per second, and consumes 120 µmol of ATP per second. We calculate:

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Thus, it will take our brains less than a half-minute before they deplete their energy stores, which corresponds closely with clinically established 1 minute time frame before brain cells begin to die due to lack of oxygen.

Therefore, if you suddenly lost all of your mitochondria, your brain will begin to die 21 seconds before Qui-Gon Jinn can finish ruining the mystique of the Force (for reference, 46 total seconds)!

 

Look forward to an upcoming post about the origins of organelles including mitochondria, chloroplasts, and maybe even midichlorians.