Mitochondrial diseases can be devastating.  The Mitochondrial foundation advises physicians to "think mitochondria" if they encounter a complex disease.

Mitochondrial diseases may involve multiple systems.

 Mitochondial Architecture

Mitochondria contain two membranes, separated by a space.  Both are the typical "unit membrane" (railroad track) in structure.  Inside the space enclosed by the inner membrane is the matrix.  This appears moderately dense and one may find strands of DNA, ribosomes, or small granules in the matrix. The mitochondria are able to code for part of their proteins with these molecular tools. The above cartoon shows the diagram of the mitochondrial membranes and the enclosed compartments.

How are mitochondria organized to be powerhouses?

The food we eat is oxidized to produce high-energy electrons that are converted to stored energy. This energy is stored in high energy phosphate bonds in a molecule called adenosine triphosphate, or ATP. ATP is converted from adenosine diphosphate by adding the phosphate group with the high-energy bond. Various reactions in the cell can either use energy (whereby the ATP is converted back to ADP, releasing the high energy bond) or produce it (whereby the ATP is produced from ADP).

Steps from glycolysis to the electron transport chain. Why are mitochondria important?

Much of this you will get in the Biochemistry lectures.  Therefore, this is only an introduction. They will  break down each of the steps so you can see how food turns into ATP energy packets and water.  The food we eat must first be converted to basic chemicals that the cell can use. Some of the best energy supplying foods contain sugars or carbohydrates ...bread, for example.  Using this as an example, the sugars are broken down by enzymes that split them into the simplest form of sugar which is called glucose.  Then, glucose enters the cell by special molecules in the membrane called “glucose transporters”. 

Once inside the cell, glucose is broken down to make ATP in two pathways.  The first pathway requires no oxygen and is called anaerobic metabolism.  This pathway is called glycolysis and it occurs in the cytoplasm outside the mitochondria.  During glycolysis, glucose is broken down into pyruvate. Other foods like fats can also be broken down for use as fuel (see following cartoon). Each reaction is designed to produce some hydrogen ions (electrons) that can be used to make energy packets (ATP).  However, only 4 ATP molecules can be made by one molecule of glucose run through this pathway.  That is why mitochondria and oxygen are so important.  We need to continue the breakdown process with the Kreb’s cycle inside the mitochondria  in order to get enough ATP to run all the cell functions. The events that occur inside and outside mitochondria are diagrammed in the above cartoon. Pyruvate is carried into the mitochondria and there it is converted into Acetyl Co-A which enters the Kreb's cycle.  This first reaction produces carbon dioxide because it involves the removal of one carbon from the pyruvate.  Please refer to Dr. Beneš' lecture for appropriate details.

How does the Kreb's cycle work?

The whole idea behind respiration in the mitochondria is to use the Kreb’s cycle (also called the citric acid or tricaboxylic acid cycle) to get as many electrons out of the food we eat as possible.  These electrons (in the form of hydrogen ions) are then used to drive pumps that produce ATP.   The energy carried by ATP is then used for all kinds of cellular functions like movement, transport, entry and exit of products, division, etc.  The following explanation is very simple and focuses on only the pathway from pyruvate through the cycle.  However, it illustrates the process and its functions. The Kreb's cycle enzymes are in the matrix.

To run the Kreb's cycle, you need several important molecules in addition to all the enzymes.  First, you need pyruvate, which is made by glycolysis from glucose. Next, you need some carrier molecules for the hydrogen ions or electrons.  There are two types of these: one is called nicotinamide adenine dinucleotide (NAD+) and the other is called flavin adenine dinucleotide (FAD+).   The third molecule, of course, is oxygen.

Pyruvate is a 3 carbon molecule. After it enters the mitochondria, it is broken down to a 2 carbon molecule, Acetyl CoA   This releases carbon dioxide.  Acetyl CoA  join with  a 4 carbon molecule called oxaloacetate to form citric acid. (2 carbons + 4 carbons = 6 carbons).  That is where the Citric acid cycle got its name. Citric acid is then broken down and modified  in a stepwise fashion to release the hydrogen ions and carbon molecules.  The carbon molecules are used to make more carbon dioxide and the hydrogen ions are picked up by the carriers: NAD and FAD (see below).  Eventually, the process produces the 4 carbon oxaloacetate again to react with more Acetyl CoA.  The reason the process is called a cycle, is because it ends up always where it started.

What is “oxidative phosphorylation”?  

First, some basic definitions.  When you take hydrogen ions or electrons away from a molecule, you “oxidize” that molecule.  When you give hydrogen ions or electrons to a molecule, you “reduce” that molecule.   When you give phosphate molecules to a molecule, you “phosphorylate” that molecule.   So, oxidative phosphorylation (very simply) means the process that couples the removal of hydrogen ions from one molecule and giving phosphate molecules to another molecule.   How does this apply to mitochondria?  This is the process that makes ATP from ADP.

Oxidation steps

As the Kreb’s cycle runs, hydrogen ions (or electrons) are donated to the two carrier molecules in 4 of the steps.  They are picked up by either NAD or FAD and these carrier molecules become NADH and FADH (because they now are carrying a hydrogen ion).  They carry the hydrogen ions to the inner mitochondrial membrane (cristae). This is where the electron transport complexes are embedded in the membrane.  The following cartoon shows what happens next.  

  The NADH and FADH essentially serve as a ferry in the lateral plane of the membrane diffusing from one complex to the next. At each complex site is a hydrogen (or proton) pump which  transfers hydrogen from one side of the membrane to the other.  This creates a gradient across the inner membrane with a higher concentration of Hydrogen ions in the intercristae space (this is the space between the inner and outer membranes).

The following cartoon shows the individual complexes in the electron transport chain.  The electrons are carried from complex to complex by ubiquinone and cycochrome C.   Cytochrome C is more mobile because it is located on the inner membrane  (in the inner cristal space). 

Phosphorylation of ADP

The third pump in the series  catalyzes the transfer of the electrons to oxygen to make water. This chemiosmotic pumping creates an electrochemical proton gradient across the membrane which is used to drive the "energy producing machine"...the ATP synthase. This molecule is found in small elementary particles that project from the cristae. The cartoon below shows an elementary particle.

As stated above, this process requires oxygen which is why it is called "aerobic metabolism". The ATP synthase uses the energy of the  hydrogen ion (also called proton) gradient to form ATP from ADP and Phosphate. The process also produces water from the hydrogen and the oxygen. Thus, each compartment in the mitochondrion is specialized for one phase of these reactions.

Review these concepts:
Where are the Kreb's cycle enzymes?
What is needed to run the Kreb's cycle?
What is produced during the Kreb's cycle?
What carries the hydrogen ions to the Electron transport chain?
Where are the electron transport chain complexes?
What does the electron transport chain do with the hydrogen ions?
Where is the ATP synthase?
How do the ATP synthase molecules use the hydrogen ions to make ATP? Where is the oxygen used?

So, why do we need mitochondria?

Importance of the cristae

You can now appreciate the importance of the cristae....not only do they contain and organize the electron transport chain and the ATP pumps, they also serve to separate the matrix from the space that will contain the hydrogen ions, allowing the gradient needed to drive the pump. When the discussion focuses on how mitochondria move proteins into the matrix, you will see another reason why this hydrogen ion (proton) gradient is so important!  

As shown in the above cartoons, the molecules in the electron transport chain are found as a cluster organized in the cristae. These membrane shelves may be more numerous in mitochondria that are more active in the production of ATP. Thus, they may increase the density of these membranes as the need arises. The flight muscle of a hummingbird has many cristae in each mitochondrion, because the need is so great. Return to Menu

Structure and function of the inner membrane and elementary particles   Mitochondria can be separated and the inner and outer membrane can be dissociated. This will result in a fraction containing only the inner membrane and the matrix. These have been called "mitoplasts". They are functional and have helped us learn more about the compartmentation of mitochondria. One can open mitoplasts and view the inside membrane surface after negatively staining the membranes. This deposits stain around any surface projections. With this method, one can see the elementary particles projecting from the inner surface of the cristae. These are the ATP synthase molecules (or elementary particles) discussed in the previous section.   Return to Menu   Learn about mitochondrial replication, DNA, lifecycle and protein transport: Learn about export from mitochondria