Mitochondria Structure Notes PDF

Last edited: 3/3/2023 5. MITOCHONDRIA STRUCTURE & FUNCTION Mitochondria Structure & Function Medical Editor: Aldrich Christiandy OUTLINE I) CELL MEMBRANE STRUCTURE II...

Last edited: 3/3/2023 5. MITOCHONDRIA STRUCTURE & FUNCTION Mitochondria Structure & Function Medical Editor: Aldrich Christiandy OUTLINE I) CELL MEMBRANE STRUCTURE III) REVIEW QUESTIONS (A) MEMBRANE LIPIDS CHECK YOUR ANSWERS (B) MEMBRANE PROTEINS IV) REFERENCES (C) GLYCOCALYX II) CELL MEMBRANE FUNCTION (A) GLYCOCALYX (B) MEMBRANE LIPIDS (C) MEMBRANE PROTEINS I) MITOCHONDRIA OVERVIEW Mitochondria are always referred to as the powerhouse of the cell. o Not only do they ATP, but there are also lots of things that mitochondria can do Mitochondria has sausage-shaped kind of like organelles. o If we zoom in on the structure, we have several different components. (1) Double-layered membrane (3) Cristae (i) Outer membrane Within the inner membrane, there’s a specific type of invaginations Made of a phospholipid bilayer o Continuation of the inner membrane but The outer membrane is very permeable invaginates into the center o Allow for things to move in and out of the mitochondria The whole purpose is to increase the surface area for a (ii) Inner membrane lot of specific types of metabolic reactions Another phospholipid bilayer (4) Mitochondrial matrix Not very permeable Bunch of different solutes in it o Has lots of selective proteins transporters that are There are two particular things in the matrix present o Very closely regulated and determine what moves in (i) Mitochondrial DNA and out of the mitochondria This is maternal DNA (only inherited from the mother) (2) Intermembrane space Has genes to make particular RNA to make proteins Space that exists between the outer and inner membrane (ii) Ribosomes Highly concentrated with proton ions (H+) o Helpful with our electron transport chain But we need certain things that help make proteins o We need ribosomes to be able to translate that RNA and make proteins o These are proteins the mitochondria can make on their own to help with their function Quick recap Structures o Outer membrane o Inner membrane o the crista, a special invagination of the inner membrane into the center Which one is highly permeable? Outer membrane Which one is less permeable? Inner membrane What’s the space between the outer and inner membrane? Intermembrane space o What is it rich in? Proton ions What is all the fluid in the center of the mitochondria? Mitochondrial matrix o Rich in mitochondrial DNA and ribosomes MITOCHONDRIA Structure & Function CELL BIOLOGY: Note #5. 1 of 6  II) MITOCHONDRIA FUNCTIONS (A) OUTER AND INNER MEMBRANE Outer and inner membrane plays a huge role in protein transport We have a cell, nucleus, free ribosomes o And we’re zooming into the mitochondria ▪ The outer and inner membrane ▪ Mitochondrial matrix Mitochondria have DNA In intermembrane space → Translocase of the inner o Mitochondrial DNA can make RNA, which can help to make some proteins membrane (TIM) o But it doesn’t make all the proteins that it needs to Little chaperone protein will bind to it and bring it to the be able to function next receptor on the inner membrane ▪ So, we have to take some proteins from the nucleus It stimulates the receptor The nucleus will help us to make RNA o It opens up the next channel translocase of the o RNA will then make proteins inner membrane (TIM) and pushes the unfolded o And these proteins have to get sent into the protein into the mitochondrial matrix mitochondria In the mitochondrial matrix Nucleus DNA makes RNA → come out via nuclear pore We probably need this protein to perform specific things o mRNA will then combine with ribosomes o Maybe it’s an enzyme that plays a role in lots of o Ribosomes will then synthesize proteins metabolic reactions ▪ These proteins are unfolded. They’re not in active form So, we have some specific types of proteases or other enzymes that will work on these proteins Translocase of the outer membrane o And properly fold him together and activate him Mitochondria has special transporters that are specialized o And make him into a specific special enzyme in moving these unfolded proteins that it needs to be able In short to perform reactions inside of the mitochondria o It needs to transport across Mitochondrial DNA only makes 15% of the protein that’s o These proteins will get chaperoned, and then they needed will bind to the little receptor o That means we need lots of proteins from the nucleus o The transporter is called translocase of the outer to help us to perform a lot of the functions membrane (TOM) Mitochondria accepts protein in unfolded form, brings them, and activates them by folding them properly Once the unfolded protein binds to the receptor o And then uses those for their metabolic reactions o It will open up TOM and move this unfolded protein into the intermembrane space (B) MISCELLANEOUS TRANSPORT Here is a quick reminder of things that are also moving across the mitochondrial membrane For metabolic reactions to occur, we have to move things right across the actual mitochondrial membrane in and out 1) Carbohydrates Remember which membrane is very permeable? Outer We’ll talk about glycolysis, or gluconeogenesis has to membrane occur inside the mitochondrial matrix Which membrane has very little permeability? Inner 2) Fatty acids membrane Because they play a role in beta-oxidation 3) Amino acids Because they play a role in the urea cycle 2 of 6 CELL BIOLOGY: Note #5. MITOCHONDRIA Structure & Function  (C) ELECTRON TRANSPORT CHAIN Very critical to the function of the mitochondria Mitochondria is often time called as powerhouse of the cell o Produces ATP o ATP is power energy Found primarily on the inner membrane o We don’t see this involved in the outer membrane o For the complete electron transport chain lecture, refer to Electron Transport Chain Part 1, Part 2, and Part 3 The basic concept here is that we have these protein molecules o They make up these different complexes like complex I-IV and a very special molecule called ATP synthase (1) Conversion of pyruvate to acetyl-CoA We take a molecule called pyruvate that gets converted Side effect into acetyl-CoA A side effect is that (2) Krebs cycle o All these electrons that are getting passed along the membrane Acetyl-CoA goes to Krebs cycle o From the Krebs cycle that occurs in the mitochondria Sometimes, some of these electrons can combine with O2 and other molecules We have high-energy electron transporters called FADH2 o H2O2 (hydrogen peroxide) and NADH o Superoxide free radicals (e.g., O2-) o They carry lots of electrons o They have them in hydrogen called hydride ion So basically, they can increase the formation of reactive oxygen species (ROS) (3) Electron transport chain – Oxidative o Which is that unfortunate side reaction from the phosphorylation electron transport chain What they do is they take, and they transport these electrons onto these proteins o They drop the electrons off in them, and then these guys pass these electrons down the chain from areas of high energy to areas of low energy Each time that happens, it pumps all these protons (H+) out into the intermembrane space o Remember, intermembrane space is very rich in H+ H+ moves down the ATP synthase pretty powerfully o It creates energy that the protein can harvest Naturally, ADP is stuck to ATP synthase o As the H+ runs down the gradient o As the electrons are being passed down ▪ It creates energies that fuse these to form ATP This process is called oxidative phosphorylation QUICK RECAP Functions to take away from the inner and outer ▪ So, they need a lot of proteins from the actual membrane nucleus Outer membrane Electron transport chain o Highly permeable o Specifically on the inner membrane Inner membrane o It takes high energy from NADH and FADH2, which o Less permeable are generated from metabolic reactions They allow for miscellaneous things to travel in and ▪ Passes it on to those things. They pass the out of the mitochondria electrons down this chain o Specifically for the metabolic reactions like ▪ And pump H+ into the intermembrane space ▪ Carbohydrates and then allows it to flow back down into the ▪ Amino acids mitochondrial matrix ▪ Fatty acids ▪ Harvesting energy to make ATP via oxidative phosphorylation They allow unfolded proteins made by the nucleus and o An unfortunate side effect that can occur is we ribosomes in the cytoplasm to be transported into the can make reactive oxygen species mitochondria o So that they can use them for their functions o They don’t make all the proteins that they need ▪ They made only 15% of the proteins and enzymes that they need MITOCHONDRIA Structure & Function CELL BIOLOGY: Note #5. 3 of 6  (D) REACTIONS THAT OCCUR IN THE MITOCHONDRIAL MATRIX We went over the inner membrane and outer membrane o How they’re particularly involved in things like protein transport, miscellaneous transport o Things like nutrients as well as some ions Also, we went over the electron transport chain o A really big function for ATP production via oxidative phosphorylation There are lots of metabolic reactions that can occur in the mitochondria o We have an inner and outer membrane, mitochondrial matrix, and cytoplasm (1) Conversion of pyruvate into acetyl-CoA (6) From the Krebs cycle, we can take some of these Whenever we bring glucose into the cell intermediates and make something called heme o Once the glucose gets into the cell, it will eventually Some of these molecules are synthesized in 2 places get converted into pyruvate via glycolysis o Mitochondrial matrix Pyruvate will get brought into the actual mitochondria o Cytoplasm o It undergoes a conversion into acetyl-CoA Quick recap (2) Krebs cycle 1) Pyruvate to acetyl-CoA Acetyl-CoA will go into the cycle called the Krebs cycle 2) Krebs cycle Coming off of the Krebs cycle is high energy molecules that carry electrons 3) 𝒃𝒆𝒕𝒂 − 𝒐𝒙𝒊𝒅𝒂𝒕𝒊𝒐𝒏𝜷-oxidation of fatty acid o NADH and FADH2 4) Urea cycle These go to electron transport chains, where they pass off It can occur in mitochondria and cytoplasm those electrons 5) Gluconeogenesis o Pump H+ into the intermembrane space o They help to generate ATP via oxidative 6) Taking something like amino acids or odd-chain fatty phosphorylation acids and converting them back into glucose Takes place in mitochondria and cytoplasm (3) 𝒃𝒆𝒕𝒂 − 𝒃𝒆𝒕𝒂 − 𝒐𝒙𝒊𝒅𝒂𝒕𝒊𝒐𝒏 7) 6) Taking something like Krebs cycle intermediates Whenever we take fatty acids and making heme o A long chain, sometimes it can be 16 carbons long o We can bring these into the mitochondrial matrix Involved in mitochondria and cytoplasm across the membrane Mnemonic They can go through a series of metabolic reactions HUG where they get broken down into acetyl-CoA o Heme synthesis o Then we can use them to make energy o Urea cycle o This step is called 𝜷- oxidation o Gluconeogenesis (4) Urea cycle 8) Ketogenesis Amino acids can be brought into the mitochondria as well We can take acetyl-CoA, and we can shunt them into Eventually, they can get metabolized and give way to making something called ketones products in the Krebs cycle o Occurs in the mitochondrial matrix o When it does that, it can give off ammonia o This process is called ketogenesis o Ammonia is really toxic The big thing that Professor Zach wants us to understand Ammonia will go through a series of reactions called is that the mitochondria are involved in a ton of metabolic the urea cycle reactions o It liberates urea which is less toxic in comparison to o It will be helpful whenever we get into biochemistry ammonia, and it’s easier to be excreted o We’ll see a lot of these reactions take place over and The urea cycle occurs specifically in the mitochondrion over again and a little bit in the cytoplasm Quick recap (5) Gluconeogenesis Protein transport We can take amino acids or odd-chain fatty acids, and we Miscellaneous transport can convert them into a specific substrate Electron transport chain ▪ We can convert them back into pyruvate and Metabolic reactions then back into glucose o There are 7 of them o 3 of them “HUG” What is it called when we take something like amino acid ▪ Heme synthesis and odd chain fatty acids and make glucose? ▪ Urea cycle Gluconeogenesis ▪ Gluconeogenesis Occurring in both the mitochondria and cytoplasm 4 of 6 CELL BIOLOGY: Note #5. MITOCHONDRIA Structure & Function  (E) APOPTOSIS Whenever there’s some process where a cell is infected or is cancerous, or it needs to die o There are special molecules present inside of mitochondrial matrix called cytochrome C o Normally, we don’t want these things to be leaking out ▪ So, there’s a protein called bcl2 that helps to prevent this from occurring In apoptosis, we decrease the number of bcl2 o Now, we can’t control the cytochrome C molecules from leaking out Cytochrome C molecules activate enzymes called caspases o Caspases are basically proteases o They start ripping through a bunch of different cells ▪ Damaging cell membranes, organelles ▪ And eventually cause the cell to undergo the death process (F) MITOCHONDRIA DNA (MTDNA) AND RIBOSOMES (1) MtDNA replication Mitochondria replication → Fission Here’s our mtDNA. We can make more of it → DNA We kind of replicate mitochondria to make more via a replication. process called fission o Important when we want to duplicate our mitochondria We can take mtDNA and undergo transcription making Mitochondria undergo a fission process RNA → make two mitochondria o RNA molecules combined with the ribosomes located o We want both of them to have an equal amount of in the mitochondria. mtDNA o These ribosomes are called 70s ribosomes ▪ The ribosomes in the cytoplasm of eukaryotic Interesting fact – Endosymbiosis theory cells are 80s Fission is a process where bacteria (prokaryotic cells) MtDNA can replicate to undergo division of the undergo division. mitochondria There’s a theory called endosymbiotic theory o Mitochondria back in the day used to just be a (2) Make RNA → transcription bacterial cell, and it would have its DNA It’s really important because we need DNA to make RNA What happens is that the bacteria gets engulfed by a We need RNA to be translated eukaryotic cell o The translation process will then synthesize o When it got engulfed inside of the eukaryotic cell, it particular types of proteins then became mitochondria o It kind of started downregulating a lot of its genes These proteins that it makes generally account for about and proteins 15% of the proteins that are needed for the mitochondria The nucleus of the eukaryotic cell became the to be able to perform their functions new factory o That means it needs a decent chunk, about 85% of It has cytoplasm to make many proteins that the proteins to come from the nuclear DNA are needed ▪ Nuclear RNA then gets translated by cytosolic And the mitochondria just primarily ribosomes “downgraded” to producing ATP and having some ▪ And they transported across the mitochondrial metabolic reactions occurring membrane MITOCHONDRIA Structure & Function CELL BIOLOGY: Note #5. 5 of 6  QUICK RECAP We’ve got through the (1) Outer & inner membrane and intermembrane space Involves in o Protein transport o Electron transport chain o Miscellaneous transport (2) And we dug into the mitochondrial matrix a little bit Metabolic reactions that occur inside the mitochondrial matrix (3) We’ve talked about how mtDNA is involved in replicating itself for the actual mitochondria to divide Or making proteins via transcription → translating those by 70s ribosomes to make proteins for it to function III) APPENDIX IV) REVIEW QUESTIONS 1) Mitochondria is a double-layered organelle where the 4) Which mitochondrial protein inhibits apoptosis? outer membrane is the least permeable, and the inner a) Bcl2 membrane is the most permeable b) Caspase a) True c) Cytochrome C b) False d) Cytochrome D 2) Which processes listed below take place in the e) Cytochrome P450 mitochondrial matrix? (May choose more than 1) V) REFERENCES a) Krebs cycle b) Electron transport chain Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017 c) 𝛽-oxidation Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: Pearson; d) Urea cycle 2020. e) Gluconeogenesis Boron WF, Boulpaep EL. Medical Physiology.; 2017. f) Protein modification Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB, Campbell NA. Campbell Biology. New York, NY: Pearson; 2020 g) Protein secretion Hahn S. (2014). Ellis Englesberg and the discovery of positive control h) Ketogenesis in gene regulation. Genetics, 198(2), 455–460. i) Heme breakdown https://doi.org/10.1534/genetics.114.167361 j) Fatty acid transport Nelson, D. L., & Cox, M. M. (2017). Lehninger principles of biochemistry (7th ed.). W.H. Freeman. 3) ATP production in mitochondria during the electron Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. transport chain process is called oxidative (2015). Molecular biology of the cell. New York: Garland Science. phosphorylation a) True b) False 6 of 6 CELL BIOLOGY: Note #5. MITOCHONDRIA Structure & Function