Mitochondria are the powerhouse of our cells that generate most of the chemical energy needed to power the cell's biochemical reactions such as cellular respiration and oxidative phosphorylation. Mitochondria contain their own DNA (that are inherited only from mother) that encodes t-RNA, r-RNA and mitochondrial proteins and use their own protein-synthesis machinery. Mitochondria are large enough to be seen in the light microscope. The number of mitochondria per cell varies widely. In humans, erythrocytes (red blood cells) do not contain any mitochondria, whereas liver cells and muscle cells may contain hundreds and thousands of mitochondria. Mitochondria play an essential role in amino acid and lipid metabolism and regulation of apoptosis. Cells protect themselves from oxidative damage by expressing a variety of antioxidant enzymes that convert ROS (Reactive Oxygen Species) into less harmful byproducts. According to the MFRTA (The Mitochondrial Free Radical Theory of Aging), mitochondria play a crucial role in mediating and amplifying the oxidative stress that drives the aging process.
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| Structure and function of mitochondria |
By the process of cellular respiration (aerobic) mitochondria produce energy from the food, which they capture and package as energy-rich molecules of ATP. That is why mitochondria are referred to as the powerhouse of the cell. Mitochondria use the process called chemiosmotic coupling to utilize the energy for biological purposes. Mitochondria occupy a substantial portion of the cytoplasmic volume of eukaryotic cells. In mitochondria, sugar metabolism is completed, and pyruvate (from glycolysis) is imported into the mitochondria and oxidized by O2 to CO2 and H2O. Each mitochondrion contains an outer membrane (that contains many porin/transport protein molecules which form channels that allow the free diffusion of molecules smaller than about 6000 Daltons), an inner membrane (which is highly convoluted that results in formation of a series of infoldings known as cristae that increase the area of inner membrane) and 2 internal compartments (matrix and intermembrane space). The matrix (that contains many identical copies of mitochondrial DNA, mitochondrial ribosomes and enzymes for mitochondrial gene expression) and the inner membrane space are the most important working stations of the mitochondrion. The matrix contains a highly concentrated mixture of enzymes that are required for oxidation of pyruvate and fatty acids to acetyl CoA and for the oxidation of acetyl CoA to CO2 by citric acid/Krebs cycle (as shown in above figure). This oxidation results in production of large amounts of NADH and FADH2. The respiratory chain/electron transport chain located in the inner mitochondrial membrane then utilizes the energy derived from electron transport to pump H+ out of the matrix to create a transmembrane electrochemical proton (H+) gradient. The electrochemical proton gradient then uses membrane bound enzyme ATP synthase to drive ATP synthesis, which is the most critical process of oxidative phosphorylation.
Chemiosmosis is used to produce ATP by oxidative phosphorylation in the electron transport chain. As a high energy electron is passed through electron transport chain some of the energy released drives the 3 respiratory enzyme complexes (The NADH Dehydrogenase complex that contains 40 polypeptide chains, the cytochrome b-c1 complex that contains 11 polypeptide chains and the cytochrome oxidase complex that contains 13 polypeptide chains) that pump out H+ from the matrix. In these complexes the electrons are transferred along a series of protein bound electron carriers including hemes and iron-sulfur centers. Electrons are carried between enzyme complexes by the mobile electron carriers ubiquinone and cytochrome-c to complete the electron transport chain.
NADH
↓
NADH dehydrogenase complex
↓
Ubiquinone
↓
Cytochrome b-c1 complex {PATH OF ELECTRON FLOW}
↓
Cytochrome-c
↓
Cytochrome oxidase complex
↓
Molecular O2
The resulting electrochemical proton gradient across the inner membrane drives H+ back through the ATP Synthase, a transmembrane protein complex that uses the energy flow to synthesize ATP from ADP. In addition to constant ATP/energy production mitochondria have many critical roles in cellular metabolism. Mitochondria generate both carbon skeletons (from sugar breakdown) and NADPH needed for cell growth. Mitochondria are also critical for buffering the redox potential in the cytosol.
Mitochondria contain their own genetic system, which is separate and distinct from the nuclear genome of the cell. Mitochondrial genomes are usually circular DNA molecules, like those of bacteria, which are present in multiple copies per organelle. The human mitochondrial genome encodes 13 proteins involved in electron transport and oxidative phosphorylation. Like the DNA of nuclear genomes, mitochondrial DNA can be altered by mutations. Such mutations have been associated with a number of diseases, e.g. Leber's hereditary optic neuropathy, a disease that leads to blindness, can be caused by mutations in mitochondrial genes that encode components of the electron transport chain. Mitochondrial DNA has an estimated 10-fold greater mutation rate than nuclear DNA and less repair capacity, and this plays an important role in aging and cancer.
References:
- The molecular biology of cell by Bruce Alberts, Alexander D. Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts and Peter Walter
- https://www.ncbi.nlm.nih.gov/books/NBK9896/#A1626
