453The inner membrane is highly convoluted, forming a series of infold-ings—known as cristae—that project into the matrix space (see Figure 14–8 and Movie 14.1). These folds greatly increase the surface area of the membrane. In a liver cell, for example, the inner membranes of all the mitochondria make up about one-third of the total membranes of the cell. And the number of cristae in a mitochondrion of a cardiac muscle cell is three times greater than that in a mitochondrion from a liver cell.The Citric Acid Cycle Generates the High-Energy Electrons Required for ATP Production The generation of ATP is powered by the flow of electrons that are derived from the burning of carbohydrates, fats, and other foodstuffs dur-ing glycolysis and the citric acid cycle (discussed in Chapter 13). These high-energy electrons are provided by activated carriers generated dur-ing these two stages of catabolism, with the majority being churned out by the citric acid cycle that operates in the mitochondrial matrix. The citric acid cycle gets the fuel it needs to produce these activated car-riers from food-derived molecules that make their way into mitochondria from the cytosol. Both the pyruvate produced by glycolysis, which takes place in the cytosol, and the fatty acids derived from the breakdown of fats (see Figure 13–3) can enter the mitochondrial intermembrane space through the porins in the outer mitochondrial membrane. These fuel mol-ecules are then transported across the inner mitochondrial membrane into the matrix, where they are converted into the crucial metabolic inter-mediate, acetyl CoA (Figure 14–9). The acetyl groups in acetyl CoA are 100 nmMatrix. This space contains a highly concentrated mixture of hundreds of enzymes, including those required for the oxidation of pyruvate and fatty acids and for the citric acid cycle. Inner membrane. Folded into numerous cristae, the inner membrane contains proteins that carry out oxidative phosphorylation, including the electron-transport chain and the ATP synthase that makes ATP. Outer membrane. Because it contains large channel-forming proteins (called porins), the outer membrane is permeable to all molecules of 5000 daltons or less. Intermembrane space. This space contains several enzymes that use the ATP passing out of the matrix to phosphorylate other nucleotides. It also contains proteins that are released during apoptosis (discussed in Chapter 18).ECB4 e14.04/14.07(A)(B)Figure 14–8 A mitochondrion is organized into four separate compartments. (A) A schematic drawing and (B) an electron micrograph of a mitochondrion. Each compartment contains a unique set of proteins, enabling it to perform its distinct functions. In liver mitochondria, an estimated 67% of the total mitochondrial protein is located in the matrix, 21% in the inner membrane, 6% in the outer membrane, and 6% in the intermembrane space. (B, courtesy of Daniel S. Friend.) Mitochondria and Oxidative Phosphorylation Sugars andpolysaccharidessugarspyruvate pyruvateFats fatty acids fatty acidsglucoseacetyl CoAMITOCHONDRIONplasma membraneCYTOSOLECB3 e13.10/13.10fatty acidsFigure 14–9 In eukaryotic cells, acetyl CoA is produced in the mitochondria from molecules derived from sugars and fats. Most of the cell’s oxidation reactions occur in these organelles, and most of its ATP is made here.QUESTION 14–2Electron micrographs show that mitochondria in heart muscle have a much higher density of cristae than mitochondria in skin cells. Suggest an explanation for this observation.The$mitochondrion:$organization455or fats. In photosynthesis, the high-energy electrons come from the organic green pigment chlorophyll, which captures energy from sunlight. And many single-celled organisms (archaea and bacteria) use inorganic substances such as hydrogen, iron, and sulfur as the source of the high-energy electrons that they need to make ATP (see, for example, Figure 1–12). Regardless of the electron source, the vast majority of living organisms use a chemiosmotic mechanism to generate ATP. In the following sec-tions, we describe in detail how this process occurs.Protons Are Pumped Across the Inner Mitochondrial Membrane by Proteins in the Electron-Transport ChainThe electron-transport chain—or respiratory chain—that carries out oxidative phosphorylation is present in many copies in the inner mito-chondrial membrane. Each chain contains over 40 proteins, grouped into three large respiratory enzyme complexes. These complexes each con-tain multiple individual proteins, including transmembrane proteins that anchor the complex firmly in the inner mitochondrial membrane.The three respiratory enzyme complexes, in the order in which they receive electrons, are: (1) NADH dehydrogenase complex, (2) cytochrome c reductase complex, and (3) cytochrome c oxidase complex (Figure 14–14). Each complex contains metal ions and other chemical groups that act as stepping stones to facilitate the passage of electrons. The movement of electrons through these respiratory complexes is accompanied by the pumping of protons from the mitochondrial matrix to the intermembrane space. Thus each complex can be thought of as a proton pump.citricacidcycleINOUTECB4 m14.09/14.10pyruvate fatty acidspyruvate fatty acidsFOOD-DERIVED MOLECULES FROM CYTOSOLATPADPATPADPNADHNAD+e–OUTO2O2CO2CO2inner mitochondrial membraneouter mitochondrial membraneATP synthaseINH+H+H+H+H2O2Pi+Pi+acetyl CoAFigure 14–12 Activated carriers generated during the citric acid cycle power the production of ATP. Pyruvate and fatty acids enter the mitochondrial matrix (bottom), where they are converted to acetyl CoA. The acetyl CoA is then metabolized by the citric acid cycle, which produces NADH (and FADH2, not shown). During oxidative phosphorylation, high-energy electrons donated by NADH (and FADH2) are then passed along the electron-transport chain in the inner membrane to oxygen (O2); this electron transport generates a proton gradient across the inner membrane, which is used to drive the production of ATP by ATP synthase. The exact ratios of “reactants” and “products” are not indicated in this diagram: for example, we will see shortly that it requires four electrons from four NADH molecules to convert O2 to two H2O molecules.Figure 14–13 Mitochondria catalyze a major conversion of energy. In oxidative phosphorylation, the energy released by