Mitochondrial functions

Although the primary function of mitochondria is to convert organic materials into cellular energy in the form of ATP, mitochondria play an important role in many metabolic tasks, such as:

- Apoptosis-Programmed cell death
- Glutamate-mediated excitotoxic neuronal injury
- Cellular proliferation
- Regulation of the cellular redox state
- Heme synthesis
- Steroid synthesis
- Heat production (enabling the organism to stay warm).

Some mitochondrial functions are performed only in specific types of cells. For example, mitochondria in liver cells contain enzymes that allow them to detoxify ammonia, a waste product of protein metabolism. A mutation in the genes regulating any of these functions can result in a variety of mitochondrial diseases.

Energy conversion

As stated above, the primary function of the mitochondria is the production of ATP. This is done by metabolizing the major products of glycolysis: pyruvate and NADH (glycolysis is performed outside the mitochondria, in the host cell's cytosol). This metabolism can be performed in two very different ways, depending on the type of cell and the presence or absence of oxygen.

Pyruvate: the citric acid cycle

Each pyruvate molecule produced by glycolysis is actively transported across the inner mitochondrial membrane, and into the matrix where it is combined with coenzyme A to form acetyl CoA. Once formed, acetyl CoA is fed into the citric acid cycle , also known as the tricarboxylic acid (TCA) cycle or Krebs cycle. This process creates 3 molecules of NADH and 1 molecule of FADH2, which go on to participate in the electron transport chain.

With the exception of succinate dehydrogenase, which is bound to the inner mitochondrial membrane, all of the enzymes of the citric acid cycle are dissolved in the mitochondrial matrix.

NADH and FADH2: the electron transport chain

This energy from NADH and FADH2 is transferred to oxygen (O2) in several steps via the electron transfer chain. The protein complexes in the inner membrane (NADH dehydrogenase, cytochrome c reductase, cytochrome c oxidase) that perform the transfer use the released energy to pump protons (H+) against a gradient (the concentration of protons in the intermembrane space is higher than that in the matrix).

As the proton concentration increases in the intermembrane space, a strong concentration gradient is built up. The main exit for these protons is through the ATP synthase complex. By transporting protons from the intermembrane space back into the matrix, the ATP synthase complex can make ATP from ADP and inorganic phosphate (Pi). This process is called chemiosmosis and is an example of facilitated diffusion. Peter Mitchell was awarded the 1978 Nobel Prize in Chemistry for his work on chemiosmosis. Later, part of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their clarification of the working mechanism of ATP synthase.

Under certain conditions, protons may be allowed to re-enter the mitochondial matrix without contributing to ATP synthesis. This process, known as proton leak or mitochondrial uncoupling, results in the unharnessed energy being released as heat. This mechanism for the metabolic generation of heat is employed primarily in specialized tissues, such as the "brown fat" of newborn or hibernating mammals.


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