Okay, stop me if you’ve heard this one— mitochondria are the powerhouse of the cell!

I know, I know. But clichés become clichés for a reason— it’s usually because they’re the easiest way to say something.

For better or for worse. Oh no, that’s another one! In this case, mitochondria really are the powerhouse of the cell.

These little organelles inside all of your trillions of cells are hard at work transferring energy from food and oxygen into the fuel you need to do everything, from texting a friend to organizing your stuffed insect collection. I mean, clearly, you can’t put the praying mantis next to the moth. Mitochondria are a key player  in cellular respiration, the process that breaks down food and oxygen so we can energize our cells.

And we often take cellular  respiration for granted. After all, it goes on behind the scenes, totally escaping our notice. But it’s a super important process for all of us multicellular, oxygen-breathing organisms.

Hi! I'm Dr. Sammy, your friendly neighborhood entomologist, and this is Crash Course Biology. [Deep Breath] Ahh, breathe  in that fresh theme music. [THEME MUSIC] Energy in our bodies is stored in the molecule ATP, or adenosine-triphosphate.

ATP is like a rechargeable battery — we fill it with energy again and again. And the energy is used to power important cellular processes — like making sure our bodies maintain homeostasis, or in other words, keeping our bodies regulated with the right balance of the stuff that we need. This is what keeps us functioning relatively stably even as the conditions around us change, like when we sweat to get rid of extra heat energy or shiver to generate more heat.

The average human needs to use over a hundred pounds of ATP a day! A hundred pounds, though! It’s a lot!

It’s a huge amount. That is my body weight, basically… In ATP. Ok, no, no, I’m good, I’m good, I’m fine, I just… you know, mind blown, now we gotta put it back together so I can do the show.

But, like money, ATP doesn’t grow on trees. Our bodies need to be constantly making and breaking down ATP in a recycling process that amounts to a full-time job for our cells. That job?

Cellular respiration. See, you, me, and all the bugs, birds, and fish between us, are aerobic organisms, which basically means we need oxygen to live and grow. And, with the help of that oxygen, our cells release energy from our food and store it in the form of ATP.

But there are also organisms, such as some bacteria, that can release and store energy without oxygen in a process called anaerobic respiration. And you have fermentation, a similar process that doesn’t require oxygen, to thank for sourdough, kombucha, and kimchi. In any case, the cellular respiration process is sort of like a million tiny little fires burning inside each of your cells.

Glucose and oxygen are the fuel in this process, coming from the air you breathe and the food you eat, especially carbohydrates. And carbon dioxide and water are the end products. Unlike a campfire, where the carbohydrates in wood burn up quickly to give off energy as heat and light, the process of breaking down food by cellular respiration releases energy relatively slowly, through many chemical reactions.

Cells do this in a controlled way so that energy is harvested to assemble ATP molecules instead of like, you know, an explosion. Yeah, as cool as it sounds, a little “fire in your belly” would be counterproductive by evolutionary standards. Cellular respiration combines a couple of metabolic pathways, or linked chemical reactions that happen in cells to complete a process.

You can think of it kind of like a Rube Goldberg machine, where one chemical reaction triggers the next, and then that one starts the next one, and so on. The whole process needs a jumpstart of ATP to get going, but eventually, at the end of cellular respiration, more ATP is produced than was needed at the start. It’s true what they say: you’ve got to spend money to make money.

So, ok, how does this remarkable system happening  all the time, within each  of our cells, actually work? Cellular respiration occurs in three main stages. It all starts with glycolysis, which breaks down the simple sugar glucose that we get from eating carbs.

See, glucose doesn’t help us much in this form —it’s not the right energy currency for the cell. The cell’s energy currency is ATP. And what do you do in a country where they don’t take your currency?

You exchange it. Shoutout to one of my former students, Catherine Fontana, for this analogy. Glycolysis is the first part of that system of currency exchange, and it happens in a cell’s cytoplasm, the jello-like goo that fills it up.

See ten different enzymes— think of them like little bank tellers— catalyze, or speed up, ten chemical reactions to break down the glucose. Each one makes a small change to the currency and hands it off to the next teller, with the last of them yielding a three-carbon chemical called pyruvate, an important transition molecule that becomes a key reactant in further processes like the citric acid cycle  or anaerobic respiration. Glycolysis results in the net production of two molecules of our target currency ATP, and it also relies on a molecule called NAD+, which you can think of as a carrier molecule.

Here at First National Bank of the Cell, we’ve got these fancy proton and electron coins that can be exchanged later for even more ATP. For safekeeping, right now we’ll just attach them to this molecule of NAD+. At the end of stage one, it hauls off two electrons and one proton to form NADH, which is used in the final step of cellular respiration.

But let’s not put the cart before the horse. Once glycolysis has finished, we begin the prep work for stage two — which will be the citric acid cycle. Our pyruvate reactant moves from the cell’s cytoplasm into the mitochondria.

Here, an enzyme continues to process the pyruvate, mining it for even more energy. It oxidizes the molecule,  basically plucking another  pair of electron coins from  it to be used later on. This step is where some of the carbon dioxide that’s produced by cellular respiration gets made.

A CO2 molecule, which we exhale, splits off of the pyruvate and leaves behind a product with just two carbons. And this new two-carbon product kickstart the next metabolic pathway involved in respiration, the citric acid cycle, also  called the Krebs cycle. When this two-carbon molecule bonds with this four-carbon molecule, oxaloacetate, they make a product with six carbons.

It's a complicated, multistep process, but long story short, a couple enzymes come along and remove two of those carbons to make two more carbon dioxide molecules, which again we exhale…I mean we’re just giving the stuff away at this point. Alongside the CO2, the citric acid cycle also produces one more ATP, three more molecules of NADH, and another transport molecule for electrons and protons called FADH2. The citric acid cycle is, well... a cycle.

So in the end we’re back to a chemical with four carbons— the exact same four-carbon molecule that we started with. Then the four-carbon molecule bonds with the next incoming two-carbon molecule – and the cycle continues. It happens twice for every glucose molecule that kickstarts cellular respiration.

Which brings us to the final step in cellular respiration — stage three, oxidative phosphorylation. This also occurs in the mitochondria and is where the bulk of ATP gets made. If the first two stages of this process were like visiting the bank, oxidative phosphorylation is like going to the Mint where money is printed!

See, mitochondria have a really neat structure that makes all of this possible. There’s an outer membrane containing large pores that can let chemicals in and out. And there’s a second membrane  folded up inside of it.

Stuck into the inner membrane, we find the huge protein complexes of the electron transport chain, which have two jobs. One is to accept the electrons from the transport molecules when they make a stop at the very inside of both membranes. After they’re dropped off, the electrons travel through the electron transport chain, where each acceptor in the pathway forms a more stable molecule than the one before it when it takes electrons.

So, each step releases energy. The chemical energy gets turned into mechanical energy that lets the protein complexes of the electron transport chain do their second job: proton pumping. Those protons that got dropped off in the matrix have somewhere they’re needed: the intermembrane space, which is what it sounds like— the space between the inner and outer mitochondrial membranes.

And the energy that’s released as the electrons move through the electron transport chain is what sends them there. So, the protons get actively  transported as a result  of the energy released from the process before. Proton pumping then puts a bunch of protons in the space between the inner and outer membranes, increasing the concentration.

This creates a proton gradient, where the amount of protons is way higher between the membranes than in the matrix. Think of it like a dam. One side of the dam is filled with a lot more water than the other.

And if we open a channel, water from the full side comes rushing in with some serious force. And this can be used to generate electricity by moving hydroelectric generators. It’s the same for the concentrated protons in the intermembrane space.

The protons have a path back into the matrix through a channel in the form of an enzyme called ATP synthase. Resembling a flower, the ATP synthase stalk is planted within the inner mitochondrial membrane. Protons enter a channel on the intermembrane space side and pass back into the matrix, moving from high concentration to low concentration in an attempt to even the proton gradient out.

The proton movement pushes ATP synthase like a merry-go-round. Providing the power that literally spins the ATP synthase, like the water rushing through a dam powers a hydroelectric generator to create electricity. The rotation causes movement up the whole stalk of ATP synthase.

In this final stage of cellular respiration, the movement of protons powers the ATP synthase, which, instead of making electricity, makes a ton of ATP— around thirty molecules for each glucose molecule we started with. So altogether, one glucose molecule has an exchange rate of about thirty ATP. And all of those remaining electrons when they’ve passed through the electron transport chain?

Well, they ultimately get passed on to two bonded oxygen atoms. And to balance the negative charges that the bonded oxygen atoms accept as electrons, they have to grab some protons too, forming our old friend water. So, I know that that’s a lot of information.

Let’s take a moment to recap all that. Cellular respiration begins outside of the mitochondria with glycolysis. Glycolysis takes glucose from the food you eat and produces pyruvate, along with a little ATP and NADH, starting the process of currency exchange.

The pyruvate moves into the mitochondria where it gets oxidized, shortening it to a two-carbon chemical. That chemical enters the citric acid cycle where enzymes further break it down, producing the carbon dioxide that we exhale. Plus, a little more ATP and NADH.

And while all of that is happening, the electrons and protons (in the form of hydrogen atoms) that are being removed during each step are hitching a ride into the mitochondria through the transport molecules NADH and FADH2. The electrons provide the energy to move protons, creating a gradient that is constantly searching for an equilibrium. All the while, the leftover electrons hitch their wagons to oxygen and create water.

As the protons move into the mitochondrial matrix, their movement powers the ATP synthase, which in turn creates a bunch of molecules of ATP. And that ATP being generated  inside the mitochondria  then powers all of our other cellular processes. And what’s even wilder, is  that all of that is happening  not only constantly, but really, really quickly.

Sure, it’s slow compared  to the reactions in a fire  or explosion but it’s really  fast by human standards. What took me a whole episode to explain happens in the blink of an eye. Around ten million ATP molecules can be generated per second in a single cell. [mind blown explosion sounds] Speaking of explosions, my mind was just blown.

The process of cellular respiration is, like many cellular processes, a complex one. But it’s also an incredibly important one. It generates the ATP molecules we use to run these complicated machines we call bodies.

And to do that, clichés aside, we need mitochondria, the powerhouse of the cell. Without those little organelles inside of all of our cells, we would be in a bad way. So thanks, mitochondria, for keeping us grooving.

Next time, we’re going to  dive into what is arguably  the most important chemical reaction on Earth. I'm talking about photosynthesis. But we’ll cross that bridge when we get there.

I’ll see you then! Deuces! This series was produced in collaboration with HHMI BioInteractive.

If you’re an educator, visit BioInteractive.org/CrashCourse for classroom resources and professional development related to the topics covered in this course. Thanks for watching this episode of Crash Course Biology which was filmed at our studio in Indianapolis, Indiana, and was made with the help of all these nice people. If you want to help keep Crash Course free for everyone, forever, you can join our community on Patreon.