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+ Mitochondria
+ Biochemistry
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Alan Bustany

What effect would you expect dinitrophenol to have on the change in pH across the inner mitochondrial membrane?

Daniel James Berger  Follow

Hi NAMASAKA!

1. Dinitrophenol has some interesting effects on the mitochondria and these effects were discovered during various research studies in the past.

Dinitrophenol or shortly DNP is a powerful uncoupler — meaning it disturb ETC and can break down the proton gradient that exists between the intermembranous space or cyroplasm and the matrix of the mitochondrion. This causes the protons to move back into the matrix, causing the pH to drop.

Since the proton gradient get collapsed, the ATP synthase cannot function normally. Therefore, the ATP synthase would no longer produce any ATP.

Hope you got answer!!

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David O'Malley  Follow

Dinitrophenol (DNP) is small, resonant, polar and (weakly) acidic. It has the unique ability to diffuse through a lipid membrane both charged and uncharged. When it is in the blood stream, it is deprotonated, since blood pH is around 7.4 and DNP’s pKa is around 4, so it carries a negative charge. Due to the resonance and inductive characteristics of the ring and nitro groups, the charge is carried so diffusely across the molecule that it behaves like a non-polar molecule, easily passing through lipid membranes. When it enters the mitochondrial matrix, where there is a high proton concentration, DNP picks up a proton. Then it can freely diffuse into the inter-membrane space, where the pH goes back to 7.4, and its proton leaves into solution.

The protron gradient between the matrix and intermembrane space is a form of potential energy that is used to power ATP synthesis, which is necessary for every cellular process to run. When DNP relocates protons, that potential energy is lost, and the cell automatically increases its metabolism (uses more nutrients - sugar, etc.) to try to compensate for its lack of energy. This is referred to as “decoupling” the electron transport chain from ATP sysnthesis.

Theoretically, this could be a great diet drug, since it forces the body to increase catabolic processes. In fact, it was used as a diet drug briefly before being taken off the market due to dire side effects. It turns out that certain organs/populations of cells are more sensitive to being deprived of energy than others - the brain and the heart, for example, don’t do particularly well when deprived of ATP. The drug increased body temperature, breathing rate, and heart rate all as a consequence of increasing metabolism, and there were some deaths.

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