1	The Architecture of Mitochondria is Essential for Mitochondrial Function
2	“…from the United Mitochondrial Diseases Foundation” “Imagine a major city with half its power plants shut down. At best, such conditions would produce a "brown out" with large sections of the city working far below optimum efficiency.
3	Apply this to your body: “Now imagine your body with one-half of its energy producing facilities shut down. The brain would be impaired, vision would be dim, muscles would twitch spastically or would be too weak to allow your body to walk or write, your heart would be weakened, and you would not be able to eat and digest your food.” “For large numbers of people, especially children, this is precisely the situation in which they find themselves due to defects in the mitochondria…. Mitochondrial diseases compromise their lives and can be fatal.”
4	“….think mitochondria” This is the watchword of the Mitochondrial foundation. They recommend activating this rule of thumb whenever: A "common disease" has atypical features that set it apart from the pack. Three or more organ systems are involved. Recurrent setbacks or flare ups in a chronic disease occur with infections.
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6	Objectives of this presentation: Correlate structure with function Mitochondrial Geography Where are different enzyme systems located How do mitochondria reproduce themselves? How do proteins enter? Mitochondrial inheritance Diseases involving mitochondria
7	Mitochondrial Compartments
8	Mitochondrial structure
9	How are mitochondria organized to be powerhouses?
10	How are mitochondria organized to be powerhouses?
11	What happens to the electrons? Electrons are then carried from Kreb’s cycle to Electron Transport Chain in cristae, Two carrier molecules transport them to the chain: nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD+) NAD⁺ + H⁺NADH FAD⁺ + 2 H⁺FADH₂ There, they are pumped with hydrogen pumps to the space between the membranes.
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14	Regeneration of NAD+ NAD+ in cytosol picks up electrons during glycolysis and is converted to NADH. NADH cannot be transported across mitochondrial inner membrane. So, to get the electrons from the cytoplasm across to the electron transport chain, the mitochondria use the malate shuttle. In the process, NAD+ is restored in the cytoplasm.
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17	Electron transport chain
18	Cartoon showing process http://bcs.whfreeman.com/lodish5e/ Log on; use narrated version to show details.
19	Cytochrome C histochemistry
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21	Trace the packets of energy Glucose has energy in chemical bonds of about 680 kcal/molecule. 90% of this is conserved in the NADH and FADH₂ Mitochondrial architecture allows by step by step transfer of electrons along the transport chain which are close together (packed) in the cristae. Each transfer allows the energy to be released in small packets and stored as the “proton-motive” force. Moving the electrons along drives the proton pumps which sets up the concentration gradient as well as the electrical potential These two ingredients are vital for the final transfer of the energy packet to ATP
22	ATP synthase
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24	Production of ATP http://bcs.whfreeman.com/lodish5e/ Log on; use narrated version to show details.
25	Export of ATP and metabolites from mitochondria Same Proton motive force that powers the ATP synthase also powers transporters for exchange of pyruvate, malate, aspartate and glutamate. Also powers the ATP/ADP antiporter coupled to the phosphate antiporter. Phosphate transporter catalyzes import of phosphate coupled to the export of OH OH binds proton to form water. ATP/ADP antiporter is highly abundant and exchanges one ADP for one ATP For every 5 protons pumped into the intercristal space, 4 are used to make ATP and one is used to power its export.
26	Elementary particles ATP synthetase
27	Is it normal to see lots of mitochondria or cristae in the mitochondria? In some regions of the body, or some types of tissue, yes. Hummingbird flight muscle [allow wing beats of 80/sec (200/sec during courtship)] Regions near sites of active transport (high energy-ATP needs).
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29	Epithelia: basolateral surface specialized for active transport.
30	Mitochondrial replication Like their bacterial precursors, mitochondria replicate their DNA and divide by splitting to form two daughter mitochondria. Mitochondria DNA replication and division occurs during interphase, before the nuclear DNA replication. Mitochondria replicate when and where needed. Feedback may be a drop in ATP.
31	Mitochondrial replication
32	What can mitochondrial DNA encode? Human mtDNA is 16,569 bp Encodes a number of mitochondrial proteins Subunits 1, 2, and 3 of cytochrome oxidase Subunits 6, 8,9 of the F_o ATPase Apocytochrome b subunit of CoQH2-Cytochrome C reductase Seven NADH-CoQ reductase subunits
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36	What RNA’s are in mitochondria? 22 tRNAs rRNA’s 16S 12S 5S¹ ___________ ¹Magalhaes, PJ; Andreu, AL, Schon EA, Evidence for the presence of 5S rRNA in mammalian mitochondria Mol Biol Cell 9: 2375-2382.
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38	Mitochondrial organizing center
39	Experiments with Yeast mitochondria Sorgo and Yaffe, J Cell Bio. 126: 1361-1373, 1994. showed the result of the removal of an outer membrane protein from mitochondria called MDM10 (from yeast). The mitochondria are able to take in components and produce membranes and matrix enzymes. However, fission is not allowed. the result is a giant mitochondrion in each yeast cell.
40	Yeast Giant Mitochondria
41	When is replication not normal? Mitochondria fail to make ATP, this signals the cell to make more Proliferation is often a sign of mitochondrial disease…attempts to compensate for inadequate supplies of energy stores Proliferation may be accompanied by production of lots of cristae…mitochondria may seem very “dark”. Again, this is a compensatory response.
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