Mitochondrial ATP synthase: architecture, function and pathology
The relationship between mitochondria and microtubules. . As these ions thread their way through the ATP synthase, they are used to drive the energetically. Boris A. Feniouk: "ATP synthase — a splendid molecular machine" Boyer and John E. Walker for the enzymatic mechanism of synthesis of ATP; and to Jens C. Skou, Mitochondrial membrane transport protein. The physiological role of dimeric/oligomeric ATP synthase is not known at present. However, there is strong evidence for a link to mitochondrial morphology .
The enzyme then undergoes a change in shape and forces these molecules together, with the active site in the resulting "tight" state shown in red binding the newly produced ATP molecule with very high affinity. Large-enough quantities of ATP cause it to create a transmembrane proton gradientthis is used by fermenting bacteria that do not have an electron transport chain, but rather hydrolyze ATP to make a proton gradient, which they use to drive flagella and the transport of nutrients into the cell.
In respiring bacteria under physiological conditions, ATP synthase, in general, runs in the opposite direction, creating ATP while using the proton motive force created by the electron transport chain as a source of energy.
The overall process of creating energy in this fashion is termed oxidative phosphorylation.
ATP synthase, F1 complex, epsilon subunit, mitochondrial (IPR) < InterPro < EMBL-EBI
The same process takes place in the mitochondriawhere ATP synthase is located in the inner mitochondrial membrane and the F1-part projects into the mitochondrial matrix. Evolution[ edit ] The evolution of ATP synthase is thought to have been modular whereby two functionally independent subunits became associated and gained new functionality. This link is tenuous, however, as the overall structure of flagellar motors is far more complex than that of the FO particle and the ring with about 30 rotating proteins is far larger than the 10, 11, or 14 helical proteins in the FO complex.
- Mitochondrial ATP synthase: architecture, function and pathology
Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP. The different types include: F-ATPases ATP synthases, F1F0-ATPaseswhich are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation mitochondria or photosynthesis chloroplasts.
They are also found in bacteria [ PMID: P-ATPases E1E2-ATPaseswhich are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes. Both the F1 and F0 complexes are rotary motors that are coupled back-to-back.
Nonetheless, the idea was so novel that it was some years before enough supporting evidence accumulated to make it generally accepted. In the remainder of this section we shall briefly outline the type of reactions that make oxidative phosphorylation possible, saving the details of the respiratory chain for later. The hydrogen atoms are first separated into protons and electrons.
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The electrons pass through a series of electron carriers in the inner mitochondrial membrane. At several steps along the way, protons and electrons are transiently recombined. But only when the electrons reach the end of the electron-transport chain are the protons returned permanently, when they are used to neutralize the negative charges created by the final addition of the electrons to the oxygen molecule Figure Figure A comparison of biological oxidations with combustion.
A Most of the energy would be released as heat if hydrogen were simply burned. B In biological oxidation by contrast, most of the released energy is stored in a form useful to the cell by means more The two electrons are passed to the first of the more than 15 different electron carriers in the respiratory chain.
The electrons start with very high energy and gradually lose it as they pass along the chain. For the most part, the electrons pass from one metal ion to another, each of these ions being tightly bound to a protein molecule that alters the electron affinity of the metal ion discussed in detail later.
Most of the proteins involved are grouped into three large respiratory enzyme complexes, each containing transmembrane proteins that hold the complex firmly in the inner mitochondrial membrane. Each complex in the chain has a greater affinity for electrons than its predecessor, and electrons pass sequentially from one complex to another until they are finally transferred to oxygen, which has the greatest affinity of all for electrons. The proteins guide the electrons along the respiratory chain so that the electrons move sequentially from one enzyme complex to another—with no short circuits.
It generates a pH gradient across the inner mitochondrial membranewith the pH higher in the matrix than in the cytosolwhere the pH is generally close to 7. Since small molecules equilibrate freely across the outer membrane of the mitochondrion, the pH in the intermembrane space is the same as in the cytosol.
It generates a voltage gradient membrane potential across the inner mitochondrial membrane, with the inside negative and the outside positive as a result of the net outflow of positive ions.
Figure The two components of the electrochemical proton gradient. The electrochemical proton gradient exerts a proton-motive forcewhich can be measured in units of millivolts mV.
In a typical cell, the proton-motive force across the inner membrane of a respiring mitochondrion is about mV and is made up of a membrane potential of about mV and a pH gradient of about -1 pH unit. How the Proton Gradient Drives ATP Synthesis The electrochemical proton gradient across the inner mitochondrial membrane is used to drive ATP synthesis in the critical process of oxidative phosphorylation Figure This is made possible by the membrane-bound enzyme ATP synthasementioned previously.
This enzyme creates a hydrophilic pathway across the inner mitochondrial membrane that allows protons to flow down their electrochemical gradient.
The ATP synthase is of ancient origin; the same enzyme occurs in the mitochondria of animal cells, the chloroplasts of plants and algae, and in the plasma membrane of bacteria and archea. Figure The general mechanism of oxidative phosphorylation.
The structure of ATP synthase is shown in Figure A large enzymatic portion, shaped like a lollipop head and composed of a ring of 6 subunits, projects on the matrix side of the inner mitochondrial membrane.
As protons pass through a narrow channel formed at the stator-rotor contact, their movement causes the rotor ring to spin. This spinning also turns a stalk attached to the rotor blue in Figure Bwhich is thereby made to turn rapidly inside the lollipop head. As a result, the energy of proton flow down a gradient has been converted into the mechanical energy of two sets of proteins rubbing against each other: Figure ATP synthase. Both F1 and F0 are formed from multiple subunits, as indicated.
A rotating stalk turns with a rotor formed by a ring of 10 to more Three of the six subunits in the head contain binding sites for ADP and inorganic phosphate.
These are driven to form ATP as mechanical energy is converted into chemical bond energy through the repeated changes in protein conformation that the rotating stalk creates. Three or four protons need to pass through this marvelous device to make each molecule of ATP. In mitochondria, many charged small molecules, such as pyruvate, ADP, and Pi, are pumped into the matrix from the cytosolwhile others, such as ATP, must be moved in the opposite direction.