Mitochondria - How it functions

[Routaran]

I was having a conversation with one of my family members about this. My biology education is limited as i did not focus on it in high school or in university.

I understand that Mitochondira are considered the "energy factories" of a cell and that the term energy factory is not an accurate description. From reading wiki, Mitochondira primary function is to produce ATP from sugars and glucose which are then transported to other parts of the cell and metabolized.
The energy is actually stored in chemical bonds within the ATP and when released, the energy is used by the cell to perform different functions.

If there is any mistake in my basic understanding thus far, please correct me. I am continuing to read Wiki about this and ATP but if anyone could provide another good source of info, i would appreciate it.

I wanted to know what exactly determines the amount of ATP a mitochondria produces?
Can this rate vary and by how much?
What are the possible effects on the cell if the amount of ATP produced is increase or decreased significantly?
I imagine that if there isn't enough ATP, the cell won't be able to survive but what happens if there is a large excess? If this is not possbile, i would like to understand why.

Thanks.

 

[madcat8000]

I was having a conversation with one of my family members about this. My biology education is limited as i did not focus on it in high school or in university.

I understand that Mitochondira are considered the "energy factories" of a cell and that the term energy factory is not an accurate description. From reading wiki, Mitochondira primary function is to produce ATP from sugars and glucose which are then transported to other parts of the cell and metabolized.
The energy is actually stored in chemical bonds within the ATP and when released, the energy is used by the cell to perform different functions.

If there is any mistake in my basic understanding thus far, please correct me. I am continuing to read Wiki about this and ATP but if anyone could provide another good source of info, i would appreciate it.

I wanted to know what exactly determines the amount of ATP a mitochondria produces?
Can this rate vary and by how much?
What are the possible effects on the cell if the amount of ATP produced is increase or decreased significantly?
I imagine that if there isn't enough ATP, the cell won't be able to survive but what happens if there is a large excess? If this is not possbile, i would like to understand why.

Thanks.

The amount of energy produced by a mitochondria can be a bit quirky, the analogy of water flowing downhill is a good analogy. A trickle of water flowing downhill carrys little pressure and so would produce very little electricty, however a large river flowing downhill would create a great amount electricity. You can't judge it on a certain number of gallons flowing, its the pressure behind each gallon.
http://ats.doit.wisc.edu/Biology/cb/ch/ch.htm
If i remember correctly the range of ATP production per molecule of glucose is between 18 and 38 ATP in bacteria.
http://student.ccbcmd.edu/courses/bio141/lecguide/unit6/metabolism/cellresp/yield.html
There isn't really a possibility of large excess because like in its production its not the amound of ATP but the difference between ATP/ADP its break down product. Each cell keeps a certain amount of ADP and trys very hard to keep as much as reasonably possible converted into ATP. ATP doesn't really exsist outside of a living environment and when kept in a very high concentration to its breakdown product, each ATP molecule is almost looking for a place to break down. This is actually how it carrys energy.

 

[Andy Resnick]

I was having a conversation with one of my family members about this. My biology education is limited as i did not focus on it in high school or in university.

I understand that Mitochondira are considered the "energy factories" of a cell and that the term energy factory is not an accurate description. From reading wiki, Mitochondira primary function is to produce ATP from sugars and glucose which are then transported to other parts of the cell and metabolized.
The energy is actually stored in chemical bonds within the ATP and when released, the energy is used by the cell to perform different functions.

If there is any mistake in my basic understanding thus far, please correct me. I am continuing to read Wiki about this and ATP but if anyone could provide another good source of info, i would appreciate it.

I wanted to know what exactly determines the amount of ATP a mitochondria produces?
Can this rate vary and by how much?
What are the possible effects on the cell if the amount of ATP produced is increase or decreased significantly?
I imagine that if there isn't enough ATP, the cell won't be able to survive but what happens if there is a large excess? If this is not possbile, i would like to understand why.

Thanks.

Our current understanding of mitochondrial function comes from Peter Mitchell's chemiosmotic theory.

Most of what you wrote is correct- mitochondria generate ATP from glucose (and other molecules) via the Krebs cycle (citric acid cycle) and the ATP is used by the cell to do things. However, the citric acid cycle couples to another process in mitochondria- oxidative phosphorylation.

http://en.wikipedia.org/wiki/Oxidative_phosphorylation

Oxidative phosphorylation is the reason ATP is used for energy, and it determines how much useful energy we get out by hydrolyzing ATP.

The chemiosmotic theory provides a mechanism to explain why we get 40 kJ/mol of energy out of ATP, and it does not have to do with a "high energy chemical bond"- that's an incorrect concept.

ATP has 'value' because there is so much of it- 10^10 more- as compared to equilibrium. That is, the relative concentration of ATP to ADP in our bodies is 10^10 higher than when we are dead. Every time we use a molecule of ATP, we move toward equilibrium a little bit, and in the process use that liberated *free energy* to perform a useful function.

We have about 0.1 mol ATP in our entire body, and our metabolism uses up about 100 mol ATP per day (50 kg). Our mitochondria work very hard to constantly generate ATP 24 hours per day. The energy mitochondria use to generate all that ATP lies in the difference in concentration of H+ on either side of the mitochondria membrane- the pH gradient is a way to store energy- the resulting potential drop across the mitochondrial membrane is about 200 mV. In some ways, mitochondria are little batteries.

ATP does more than serve as 'energy currency'- it's also a signaling molecule:

http://en.wikipedia.org/wiki/Adenosine_triphosphate

When there's not enough ATP around, the cell (for example a muscle cell) fatigues. Cyanide blocks the oxidative phosphorylation process by binding to cytochrome c oxidase and death occurs.

 

[Routaran]

Thanks for the great info there. I apologise for not replying sooner.

So if i understand this correctly:
We have a set amount of ATP in our body ~0.1mol.
ATP is converted to ADP which releases energy which the cell then uses to do other useful tasks.
Our body ses 100mol of ATP per day.
The mitochondria are constantly converting the ADP waste product back into usable ATP to keep up with the body's demand.
The primary factor that determins the ability of the mitochondia to convert ADP to ATP is its access to H+ ions.
The H+ ions move across the electric potenial drop (approx 200mV) and this electrical energy is what's used add an extra phospate and convert the ADP to the ATP.

Cells monitor the ration between ATP and AMP and use this to regulate the production and consumption of ATP.

If the ratio of ATP:ADP gets low, cells fatigue and eventually die.

what happens if the ratio gets excessively large? say 10x normal. any ill effects?
Does the ATP simply start breaking down into ADP on its own (if so what happens to the excess energy?)
Or the cell simply slows down the production of ATP till the excess is used?
Or is this possibility so extremely unlikely to happen because of the already vast difference in concentration of ATP & ADP that there'll never be enough ADP present in the mitochondria to allow this to happen therefore not worth discussing?

Also, what generally supplies the H+ ions?

 

[Andy Resnick]

Thanks for the great info there. I apologise for not replying sooner.

So if i understand this correctly:
We have a set amount of ATP in our body ~0.1mol.
ATP is converted to ADP which releases energy which the cell then uses to do other useful tasks.
Our body ses 100mol of ATP per day.
The mitochondria are constantly converting the ADP waste product back into usable ATP to keep up with the body's demand.
The primary factor that determins the ability of the mitochondia to convert ADP to ATP is its access to H+ ions.
The H+ ions move across the electric potenial drop (approx 200mV) and this electrical energy is what's used add an extra phospate and convert the ADP to the ATP.

According to what I was taught, that's essentially correct. The chemisomotic mechanism allows energy to be stored as an osmotic gradient and converted into chemical reactions.

Cells monitor the ration between ATP and AMP and use this to regulate the production and consumption of ATP.

If the ratio of ATP:ADP gets low, cells fatigue and eventually die.

what happens if the ratio gets excessively large? say 10x normal. any ill effects?
Does the ATP simply start breaking down into ADP on its own (if so what happens to the excess energy?)
Or the cell simply slows down the production of ATP till the excess is used?
Or is this possibility so extremely unlikely to happen because of the already vast difference in concentration of ATP & ADP that there'll never be enough ADP present in the mitochondria to allow this to happen therefore not worth discussing?

Also, what generally supplies the H+ ions?

I think of the membrane potential (the gradient in [H+]) as the primary source of energy- the 'set point'. Since H+ has a charge, the osmotic gradient is also an *electrical*potential gradient; the two are conceptually interchangable. The membrane potential sets the steady-state concentration of ATP; in order to generate an excess of ATP, the membrane potential must be increased. I do not know of any mitochondrial disorder where this occurs, but someone else may know more.

H+ ions come from lots of places; think pH: acids and bases.

 

[Ygggdrasil]

Also, what generally supplies the H+ ions?

As has been mentioned in this thread, the movement of H⁺ ions from the intermembrane space of the mitochondria to the mitochondrial matrix supplies the energy for ATP synthesis. This movement of H⁺ ions can be used to drive ATP synthesis because the concentration of H⁺ ions is much higher in the intermembrane space than in the matrix. Both a chemical gradient (higher concentration of H⁺ ions in the intermembrane space than in the matrix) and an electrical gradient (more positive charges in the intermembrane space than in the matrix) provide the energy to power ATP synthesis.

What creates this imbalance of H⁺ ions between the intermembrane space and the mitochondrial matrix? Here's where the electron transport chain is connected to the other steps of the central metabolic pathways. Both glycolysis and the citric acid cycle, which act sequentially to break glucose down into carbon dioxide, convert low energy NAD⁺ molecules into high energy NADH molecules. At the mitochondrial inner membrane (which separates the intermembrane space and the mitochondrial matrix), there are proton pumps which use the energy stored in NADH to pump protons from the mitochondrial matrix into the intermembrane space. These pumps convert NADH back into NAD⁺ so that the NAD⁺ can be used again in glycolysis and the citric acid cycle.

Therefore, it is the proton pumps in the mitochondrial inner membrane, powered by the conversion of NADH into NAD⁺, that supplies the gradient of H⁺ ions required for ATP synthesis.

what happens if the ratio gets excessively large? say 10x normal. any ill effects?
Does the ATP simply start breaking down into ADP on its own (if so what happens to the excess energy?)
Or the cell simply slows down the production of ATP till the excess is used?
Or is this possibility so extremely unlikely to happen because of the already vast difference in concentration of ATP & ADP that there'll never be enough ADP present in the mitochondria to allow this to happen therefore not worth discussing?

At this point, it should be clear that one can regulate ATP synthesis by controlling the size of the H⁺ gradient. The cell accomplishes this by controlling the amount of NADH available to the proton pumps that establish the H⁺ gradient. Many of the key enzymes in glycolysis and citric acid cycle that act at important bottlenecks in the process are in fact regulated by the ATP/ADP ratio. The presence of too much ATP will inhibit these enzymes and slow down the production of NADH, while too little ATP or too much ADP will cause the enzymes to speed up the production of NADH.

The abilities of these metabolic enzymes to sense the ATP/ADP ratio and increase/decrease the rate at which glucose is consumed allows the cells to very tightly regulate the amount of ATP and ADP in the cell such that the ATP/ADP ratio does not vary much.

 

[Routaran]

I think I have a much better understanding of how mitochondria work and cleared up some earlier misconceptions. Next up for me is to read and learn about the Glycolysis and citric acid cycle to understand just how the regulation is implemented.

Thank you all very much for the education :)

I guess the last question is if there are any documented cases of a disorder that disrupts the ratio of ATP/ADP in humans or any other species?

 

[Pythagorean]

http://www.johnkyrk.com/