Saturday, November 13, 2010

The Mitochondrion: A story of a little cell organelle

The mitochondrion is perhaps the most fascinating organelle in the eukaryotic cell. Under the electron microscope, each mitochondrion appears sausage-shaped, or you may call it worm-shaped, from one to many micrometres long; each is enclosed in two separate membranes. The inner membrane is thrown into finger-like folds called ‘cristae’, projecting inward. Inside the double-wall, are scattered many tiny dot-like ribosomes. Remarkably, the mitochondrion even has its own DNA! And yeah, it multiplies itself.
We broke open the cell and spun the soup of cell fragments in a centrifuge- this separated the cell organelles according to their size, shape and density. We now tested the purified mitochondria to see what chemical process they could perform. And we discovered that they oxidised sugar to produce adenosine triphosphate (ATP) - the basic chemical fuel that powers most of the cell’s activities. So the mitochondria are generators of chemical energy for the cell!

And in the process, they consume oxygen and release carbon dioxide- this indeed is respiration at the cellular level. The fact is further confirmed by the observation that mitochondria are particularly concentrated in those part of the cell that use up more energy, like the contractile apparatus of the cardiac muscle cell or the tail of the sperm cell.

So how is it that the food that we eat ultimately reaches the mitochondria which release energy from it?
All that we eat primarily consists of carbohydrates and fats. Our food is broken down to these fundamental units by our digestive system before reaching each cell.

Inside the cytoplasm, glucose and other carbohydrates are oxidised to pyruvate in a process known as glycolysis, a kind of fermentation or partial oxidation, producing two ATP molecules per glucose molecule. Fats are converted into fatty acids. This is the beginning.

This pyruvate and fatty acid dissolved in the cytosol freely enters the bilipid outer membrane of the mitochondrion through wide aqueous channels in it formed by the transport protein called ‘porin’, to reach the inter-membrane space between the outer membrane and the inner membrane. Due to high permeability of the outer membrane the inter-membrane fluid is very similar to the cytosol. In addition, it contains several enzymes that use the freshly-prepared ATP to phosphorylate other nucleotides.

Our food then reaches the inner membranes whose folded walls greatly increase the surface area of the membrane. Unlike other membranes in the cell, this membrane is impermeable to the passage of ions and most small molecules.....except where a path is provided by membrane transport proteins. It also has many other important proteins that participate in the energy production process. As a consequence of the limited permeability of the inner membrane, the fluid inside, called the ‘matrix’, is highly specialised in its contents. This is where our pyruvate and fatty acids reach. And this is where the REAL STUFF takes place.
In the mitochondrial matrix, pyruvate and fatty acids- the fuel molecules- are converted to the crucial metabolic intermediate acetyl CoA by enzymes located in the matrix. In this form, our food enters the Kreb’s Cycle, more often called the Citric Acid Cycle.

Although this cycle is considered to be a part of the aerobic metabolism, it does not itself use molecular oxygen. The cycle converts the carbon atoms in acetyl CoA to carbon dioxide, which is released from the cell as a waste product. The rest of the molecule is converted to activated NADH and FADH2- the high energy electron molecules. These molecules are transferred to the inner mitochondrial membrane, where they enter the electron-transport chain- it starts off with the formation of NAD+ and a high energy electron. This electron zigzags its way through a series of electron carriers on the inner mitochondrial membrane and finally reacts with exported molecular oxygen (this is where O2 comes into the picture during respiration) to form water. The energy released by the electron during its journey through the electron transport chain is harnessed to pump protons outside, across the inner mitochondrial membrane, thus producing an electrochemical proton gradient- an uneven distribution of proton inside and outside the inner mitochondrial membrane. This configuration stores a vast amount of potential energy.

The protons are then allowed to flow back across the membrane, down their electrochemical gradient, through a protein complex called ATP synthase, which catalyzes the energy-requiring synthesis of ATP from ADP and inorganic phosphate (Pi) in the matrix. This enzyme serves the role of a turbine, permitting the proton gradient to drive the production of ATP. The linkage of electron transport, proton pumping and ATP synthesis is known as chemiosmotic coupling. This, plus the process of consumption of O2, together is known as Oxidative Phosphorylation. This process is so efficient that it produces thirty molecules of ATP for every molecule of glucose.

ATP- this is the fate of most part of the things that we eat. It is the energy currency of the cell- the form in which energy is stored in the cell. This energy can be utilised to do work anytime, converting ATP back to ADP. And the cycle goes on......

Developments in research have enabled us to have a greater insight into the mitochondrial structure, function, and evolution. Mitochondria have been found to contain their own DNA, RNA and a complete transcription and translation system including ribosomes, which allows them to synthesise some of their own proteins. Mitochondria move about in the cell along the thread-like microtubules of the cytoskeleton. They may also remain fixed in one cellular location to target ATP directly to a site of unusually high ATP consumption. They can also multiply rapidly within the cell when there arises a need for greater energy production.

The earliest cells may have produced ATP by breaking down organic molecules left by earlier geochemical process, using some form of fermentation. Over the time, some bacteria developed much more efficient methods for generating energy and synthesizing ATP, similar to the mitochondrial mechanisms that we know today. The history of evolution of such bacteria is indeed very interesting- but that is another long story. All we need to understand is that these bacteria evidently had an advantage over the other unicellular organisms which still depended on the inefficient process of glycolysis to produce energy.

It was a lucky accident when one of our single-celled eukaryotic ancestors gulped down one of these bacteria, and decided to keep it, and christened it- Mitochondrion. Ever since, the mitochondrion has become an integral part of the eukaryotic cell, producing energy in a symbiotic relationship. Today, the mitochondria in our cells have become much more specialised for energy production. Still, it has retained its individuality- its own DNA, and a double-membrane- one belonging to the bacterium, another provided by the cell.

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