MITOCHONDRIA

1. MITOCHONDRIA (Powerhouse of the Cell)

2. Mitochondria (singular, mitochondrion) – are typically tubular or rod-shaped organelles found in the cytoplasm of most cells and produces enzymes for the metabolic conversion of food to energy. • Mitochondria are unusual organelles. They act as the power plants of the cell, are surrounded by two membranes, and have their own genome. They also divide independently of the cell in which they reside, meaning mitochondrial replication is not coupled to cell division. Some of these features are holdovers from the ancient ancestors of mitochondria, which were likely free-living prokaryotes. • Mitochondria are responsible for converting nutrients into the energy-yielding molecule adenosine triphosphate (ATP) to fuel the cell's activities.

3. Origin of Mitochondria • Mitochondria are thought to have originated from an ancient symbiosis that resulted when a nucleated cell engulfed an aerobic prokaryote. • The engulfed cell came to rely on the protective environment of the host cell, and, conversely, the host cell came to rely on the engulfed prokaryote for energy production. • Over time, the descendants of the engulfed prokaryote developed into mitochondria, and the work of these organelles — using oxygen to create energy — became critical to eukaryotic evolution

4. STRUCTURE A mitochondrion contains outer and inner membranes composed of phospholipid bilayers and proteins. The two membranes have different properties. Because of this double-membrane organization, there are five distinct parts to a mitochondrion.

5. Outer Membrane • encloses the entire organelle, has a protein-to-phospholipid ratio similar to that of the eukaryotic plasma membrane. • contains large numbers of integral proteins called porins. • allow molecules to freely diffuse.

6. Intermembrane space • is the space between the outer membrane and the inner membrane. • It is also known as Perimitochondrial space. • Because the outer membrane is freely permeable to small molecules, the concentrations of small molecules such as ions and sugars in the intermembrane space is the same as the cytosol.

7. Inner membrane • Inner membrane has much more restricted permeability, much like the plasma membrane of a cell. • The inner membrane is also loaded with proteins involved in electron transport and ATP synthesis. • This membrane surrounds the mitochondrial matrix, where the citric acid cycle produces the electrons that travel from one protein complex to the next in the inner membrane. At the end of this electron transport chain, the final electron acceptor is oxygen, and this ultimately forms water (H20). At the same time, the electron transport chain produces ATP. (This is why the the process is called oxidative phosphorylation.) • During electron transport, the participating protein complexes push protons from the matrix out to the intermembrane space. This creates a concentration gradient of protons that another protein complex, called ATP synthase, uses to power synthesis of the energy carrier molecule ATP . • The inner membrane contains fusion and fission proteins

8. At the inner mitochondrial membrane, a high energy electron is passed along an electron transport chain. The energy released pumps hydrogen out of the matrix space. The gradient created by this drives hydrogen back through the membrane, through ATP synthase. As this happens, the enzymatic activity of ATP synthasesynthesiszes ATP from ADP.

9. Fission and fusion process • Mitochondria continually change shape through the combined actions of fission, fusion, and movement along cytoskeletal tracks. • The lengths of mitochondria and the degree to which they form closed networks are determined by the balance between fission and fusion rates. • These rates are influenced by metabolic and pathogenic conditions inside mitochondria and by their cellular environment. Fission and fusion are important for growth, for mitochondrial redistribution, and for maintenance of a healthy mitochondrial network. • In addition, mitochondrial fission and fusion play prominent roles in disease-related processes such as apoptosis and mitophagy. Three members of the Dynamin family are key components of the fission and fusion machineries. • Their functions are controlled by different sets of adaptor proteins on the surface of mitochondria and by a range of regulatory processes. Here, we review what is known about these proteins and the processes that regulate their actions.

10. Matrix • The matrix is the space enclosed by the inner membrane. • It contains about 2/3 of the total protein in a mitochondrion. • The matrix is important in the production of ATP with the aid of the ATP synthase contained in the inner membrane. • The matrix contains a highly concentrated mixture of hundreds of enzymes, special mitochondrial ribosomes, tRNA, and several copies of the mitochondrial DNA genome. Of the enzymes, the major functions include oxidation of pyruvate and fatty acids, and the citric acid cycle.

11. Is the Mitochondrial Genome Still Functional? • Mitochondrial genomes are very small and show a great deal of variation as a result of divergent evolution. Mitochondrial genes that have been conserved across evolution include rRNA genes, tRNA genes, and a small number of genes that encode proteins involved in electron transport and ATP synthesis. The mitochondrial genome retains similarity to its prokaryotic ancestor, as does some of the machinery mitochondria use to synthesize proteins. In fact, mitochondrial rRNAs more closely resemble bacterial rRNAs than the eukaryotic rRNAs found in cell cytoplasm. In addition, some of the codons that mitochondria use to specify amino acids differ from the standard eukaryotic codons.Still, the vast majority of mitochondrial proteins are synthesized from nuclear genes and transported into the mitochondria. These include the enzymes required for the citric acid cycle, the proteins involved in DNA replication and transcription, and ribosomal proteins. The protein complexes of the respiratory chain are a mixture of proteins encoded by mitochondrial genes and proteins encoded by nuclear genes. Proteins in both the outer and inner mitochondrial membranes help transport newly synthesized, unfolded proteins from the cytoplasm into the matrix, where folding ensues

12. Protein import into a mitochondrian A signal sequence at the tip of a protein (blue) recognizes a receptor protein (pink) on the outer mitochondrial membrane and sticks to it. This causes diffusion of the tethered protein and its receptor through the membrane to a contact site, where translocator proteins line up (green). When at this contact site, the receptor protein hands off the tethered protein to the translocator protein, which then channels the unfolded protein past both the inner and outer mitochondrial membranes.