Why Mitochondria are the Powerhouse of the Cell.
Learn on a molecular level how the microscopic yet mighty mitochondrion keeps you energised!
It has long been taught in GCSE Biology that mitochondria are the “powerhouses” of the cell. But what does that actually mean? Why has this expression arisen to describe mitochondria?
At school, the answer to these questions was ‘mitochondria produce energy’. This is true, but what really is energy in your body? And, most importantly, how are these tiny mitochondria producing this energy?
Instead of sitting on this incredibly vague explanation that is routinely dished out at school on a grainy, black and white worksheet, lets delve deeper into the wondrous world of molecular biology and explore these questions.
I believe that everyone should know in some detail how their body is producing the energy keeping them alive. It is mind-boggling that mitochondria, whose average diameter is less than 3μm, are what’s enabling you to read this article right now, by powering almost every single chemical reaction taking place in your body. Talk of small but mighty!
So, let’s give the mitochondria the explanation they deserve.
The energy currency of cells is a molecule called Adenosine Triphosphate, or ATP for short. ATP is produced by mitochondria in the process of aerobic cellular respiration. ATP captures metabolic energy in the form of high energy phosphate bonds.
The diagram above shows the structure of ATP. ATP is made up of the nitrogenous base adenine (blue), a ribose sugar (green), and three serially bonded phosphate groups (TRI-phosphate makes sense now). These phosphate groups are what we are interested in.
When the terminal high energy phosphate bond is broken (yellow star on diagram) logically, Adenosine DI-phosphate (ADP) is formed (plus a free phosphate group), and energy from the phosphate bond is transferred to metabolic reactions.
So ATP is the form that metabolic energy takes, but how are we producing it?
Aerobic respiration can be broken down into 4 steps: Glycolysis, Link Reaction, The Citric Acid Cycle (TCA cycle) and finally Oxidative Phosphorylation. Glycolysis and the TCA cycle both produce ATP, but 90% of ATP production happens in the final step, oxidative phosphorylation. Let’s look at each step in turn to see how mitochondria produce ATP to power our bodies.
I might be about to scare you with this diagram of glycolysis. If I do, don’t panic, there are only a few key parts we need to understand what is happening so stick with me!
So, this is the first step of respiration. My main reason for including this diagram is to illustrate just how complex a small section of a larger process can be, you don’t need 90% of this diagram to understand the overall picture.
Begin by taking a look at our starting ingredient, glucose. Glucose is a sugar with the molecular formula C₆H₁₂O₆ (sound familiar from GCSE?). It is the most abundant monosaccharide and you obtain it from most foods you eat. It is the founding molecule of energy production.
At the other end, we have the product of glycolysis, a molecule called pyruvate. For every glucose you put in, you get 2 pyruvate out (denoted by the (2)). Pyruvate is an intermediate in the process of respiration and is the starting ingredient for the next step.
You can see in the products box we also make a few other molecules along the way. 2 ATP is produced (NET as we produce 4 ATP but 2 ATP are used over steps 1 and 3), this is small proportion of the total ATP made in respiration. But, its a start.
The other product is a molecule called NADH. NADH is an electron carrier, i.e. it accepts electrons to become ‘activated’ and carries them to sites of chemical reactions (the ‘inactive’ form is called NAD+), it’s a temporary energy store between the steps in respiration. It plays a key role in our bodies making energy, as we will see later.
A note to remember is that glycolysis doesn’t actually take place within the mitochondria, it happens in the cytosol (the fluid which makes up the inner volume of the cell).
So, glycolysis. We put a glucose molecule in, and get 2 pyruvate, 2 ATP and 2 NADH out. Let’s see what happens next.
The second step in respiration is the link reaction.
In this digram we can see our glucose being transported into the cytosol, where it then takes part in glycolysis and pyruvate is produced. Pyruvate is then transported over the mitochondrial membranes and into the mitochondrial matrix.
The link reaction is the conversion of pyruvate to a new molecule called Acetyl Coenzyme A. This is carried out by the pyruvate dehydrogenase complex.
Pyruvate is a 3 carbon molecule, Acetyl CoA is a 2 carbon molecule. Therefore, each pyruvate loses a carbon atom which is released as carbon dioxide.
The now 2 carbon pyruvate molecule is oxidised, which means it loses electrons. It donates these to our trusty friend NAD+ to produce NADH. Finally, Coenzyme A is added to the 2 carbon pyruvate molecule forming Acetyl CoA. So our equation is…
Pyruvate + NAD+ + CoA —> Acetyl CoA + NADH + CO2
Since each glucose molecule gives 2 pyruvate, this reaction happens twice per glucose. So we get 2 Acetyl CoA, 2 NADH and 2 CO2 produced per glucose.
The third step is the TCA cycle, also known as the Krebs Cycle. In this circular pathway, Acetyl CoA is oxidised to produce CO2 and more electrons are passed to NAD+ and another electron carrier called FAD. This produces more NADH and FADH2 (activated form of FAD) which are vital to large scale ATP production in the final step of respiration.
The takeaway from this is, again, the products. Acetyl CoA enters and each cycle generates 3 NADH, 1 FADH2, 1ATP and 2 CO2. The products per glucose are double this (as listed in the diagram) because we make 2 Acetyl CoA per glucose (one from each pyruvate generated from one glucose molecule), so each glucose turns the cycle twice. This happens in the mitochondrial matrix.
So, a review so far: Overall, per glucose we have made:
- 2 ATP and 2 NADH in glycolysis (in cytosol)
- • 2 NADH by pyruvate dehydrogenase complex (for 2 pyruvates)
- • 6 NADH, 2 FADH2 , 2 ATP in citric acid cycle (2 turns of cycle)
- • Total = 4ATP, 10 NADH, 2 FADH2 per glucose
Now we have reached the final stage! If you are still with me, we are almost there!
Oxidative phosphorylation (or the electron transport chain, ETC) is a crucial process in cellular respiration that occurs over the inner membrane of the mitochondria. It involves a series of protein complexes embedded in the inner mitochondrial membrane. High-energy electrons (2e-) stored by electron carriers NADH and FADH2 from the 3 previous metabolic reactions are shuttled along the complexes. This releases energy and driving the synthesis of ATP by pumping protons (hydrogen ions) into the space between the inner and outer mitochondrial membranes.
Complexes 1 and 3 both use the energy from donated electrons to pump 4 protons into the intermembrane space. Complex 4 pumps 2 protons and uses two protons in the reaction shown underneath. In this reaction, oxygen is termed the ‘terminal electron acceptor’, and reacts to release water at the end of the pathway.
As you might guess, the proton pumping creates a higher concentration of protons in the intermembrane space compared to the matrix of the mitochondria. This forms an electrochemical gradient which wants to pull protons back to the matrix. It is this gradient that provides the power for the synthesis of ATP.
On the right of the diagram, you can see another protein called ATP synthase. It contains a transmembrane proton carrier. Proton flow back to the mitochondrial matrix through the carrier causes a rotor inside the protein to rotate. The mechanical energy is used to form ATP from ADP and Pi.
3 protons are used by ATP synthase, plus another proton used for the Pi transporter, to make 1 ATP. Therefore, it takes 4 protons to make 1 ATP. As seen in the diagram, for every NADH that enters the ETC in complex 1, 10 protons are pumped, so 2.5 ATPs are made. (FADH2 can also donate to the ETC, but you can see as it enters in complex 2, only 6 protons are pumped, so 1.5 ATPs are made).
Per glucose we made 10 NADH and 2 FADH2, therefore we pumped 100 protons from NADH and 12 from FADH2. 112/4 = 28 ATP made in oxidative phosphorylation per glucose. Plus our 2 ATP made in glycolysis and 2 ATP made in two rotations of the TCA cycle we made 32 ATP per glucose molecule!
(Though if you want to be really nitty gritty, it is usually 30 ATP per glucose, as the NADH made in the cytosol in glycolysis requires energy for transport into the mitochondria to reach the ETC, so it produces fewer ATP then NADH made in the mitochondrial matrix)
I hope you enjoyed this wondrous ride through your cellular respiratory pathway! Hopefully this has added a digestible layer of complexity to your knowledge of energy production. A working muscle cell consumes about 10 million molecules of ATP a second, each day you can consume your own body weight in ATP. How incredible is that?!
It blows my mind to think that in every one of my trillions of tiny cells, this process is happening millions of times a second, but perhaps most staggeringly that it is just one process amongst the billions of other reactions occurring at the same time. It’s utterly amazing.
If you have any thoughts, please leave them below!
