Audio- Organelles: Episode I

Transcript

00:00 --> 00:03Yale podcast network.
00:05 --> 00:08Hello and welcome to another episode of the Yale Journal Biology.
00:08 --> 00:18and Medicine podcast YJBM is a pubmed and index quarterly Journal edited by Yale Medicine graduate and professional students and peer reviewed by experts in the fields of biology and
00:18 --> 00:23Medicine each issue of the Journal is devoted to a focused topic and through a few episodes of this podcast.
00:23 --> 00:25We would take you through the past,
00:25 --> 00:28present, and future of the issue subject matter.
00:28 --> 00:34This episode is part of our series devoted to our September 2019 issue on organelles on your cohost Kelsie Cassell,
00:34 --> 00:36a second year graduate student Epidemiology.
00:36 --> 00:44And I'm a Emma carley a second year graduate student and cell biology later on will also be joined by Amelia Hallworth a third year graduate student in Microbiology.
00:44 --> 00:51In this episode. We were talking exclusively about one of the organelles featured in the September 2019 issue on organelles the mitochondria.
00:51 --> 00:53All cells are composed of organelles,
00:53 --> 01:00which complete different functions within the cell mitochondria is a double membrane organelle known as the powerhouse of the cell,
01:00 --> 01:05which is a description often perpetuated in high school biology books to help with memorization.
01:05 --> 01:08However, this description is not new and it originated over 60 years ago.
01:08 --> 01:18The first published manuscript to announce that mitochondria is the powerhouse of the cell was written by Doctor Phillip Siekevitz and published in the Scientific American in 1957.
01:18 --> 01:25However, research on mitochondria began almost exactly a century before this powerhouse statement was made.
01:25 --> 01:29Mitochondria was originally discovered by physiologist,
01:29 --> 01:32Albert von Kölliker in 1857. and in 1886
01:32 --> 01:35It was first coined as a bio blast by scientists.
01:35 --> 01:38Richard Altman. bio blast is easily
01:38 --> 01:40a better name than mitochondria,
01:40 --> 01:50yet here we are. Some records also credit Altman with the discovery or at least ability to consistently recognize and characterize the mitochondria.
01:50 --> 01:57Mitochondria were officially renamed as mitochondria by Carl Benda in 1898. mitochondria stems from the Greek word.
01:57 --> 02:05Mitos for thread And Congress for gradual referencing the similarity in appearance to structure seen in Spermato-Genesis.
02:05 --> 02:11In 1900, a super vital stain for mitochondria was discovered which is called Janus Green B. Janus
02:11 --> 02:15green b changes color depending on the amount of oxygen present,
02:15 --> 02:17and around it around the stain.
02:17 --> 02:20It changes from blue in the presence of oxygen.
02:20 --> 02:29And pink in the absence because of this that is able to indicate the presence of mitochondria as mitochondria uses oxygen and many of its cellular processes.
02:29 --> 02:32Despite the discovery of a reliable stain to identify mitochondria.
02:32 --> 02:40The processes behind why the stain is effective an what the underlying roll mitochondrion ourselves was not known until many years later.
02:40 --> 02:51OK, So what are mitochondria doing in ourselves First off I want to dispel a myth about mitochondria so not only do high school biology textbooks.
02:51 --> 02:56Perpetuate this idea that the mitochondria is the powerhouse of the cell,
02:56 --> 03:01but they also perpetuate the idea that mitochondria are small.
03:01 --> 03:03Bean shaped organelles. But in reality,
03:03 --> 03:11mitochondria are dynamic structures capable of forming very extensive networks all throughout the cell.
03:11 --> 03:14These mitochondria can undergo Fusion and fission events,
03:14 --> 03:17so if you have a lot of fission events,
03:17 --> 03:19meaning the mitochondria, breaking up,
03:19 --> 03:20then if you look at them,
03:20 --> 03:23they might look like little beans,
03:23 --> 03:26but most of the time mitochondria are in these very amazing.
03:26 --> 03:36Dynamic networks and so overall mitochondria are way more complicated than just a bunch of little bean shapes floating around inside of cells.
03:36 --> 03:43So Kelsie just talked about how these organelles were first discovered and came to be known as the powerhouse of the cell.
03:43 --> 03:48But what exactly does powerhouse of the cell mean at the biological level.
03:48 --> 04:00This basically means that mitochondria make ATP. ATP stands for adenosine triphosphate and it's a very high energy molecule that our bodies used to store that energy that we get
04:00 --> 04:03from food to be used later.
04:03 --> 04:09ATP is made by a specialized group of proteins that all reside in the mitochondria.
04:09 --> 04:14Most of these proteins are part of something called the electron transport chain.
04:14 --> 04:22The electron transport chain uses high-energy molecules made during the breakdown of sugars in our food.
04:22 --> 04:32And, combined this with oxygen to create a gradient of positively charged hydrogen ions across the membrane of the mitochondria.
04:32 --> 04:43The protein ATP synthase, then uses this positively charged hydrogen gradient to make ATP from ADP and an inorganic phosphate.
04:43 --> 04:51For every one molecule of the sugar glucose an 6 molecules of oxygen you can get 36 ATP so this process is very,
04:51 --> 04:57very good at generating energy from the sugars and fats that are found in our food.
04:57 --> 05:03Can you still make ATP if you don't have enough oxygen like when you're exercising yeah,
05:03 --> 05:08so ATP synthase that very last step that happens in the mitochondria.
05:08 --> 05:13Only makes 32 of the 36 ATP that you get from every glucose molecule.
05:13 --> 05:18The rest come from steps that occur in the cytosol of the cell,
05:18 --> 05:21which are anaerobic and don't require oxygen,
05:21 --> 05:31however, as you can see you would only get 4 Atps if you were to just rely on that process so making ATP using oxygen and using all these cool
05:31 --> 05:36proteins found in the mitochondria is a way more energy efficient,
05:36 --> 05:39you can get lots. More energy out of your food.
05:39 --> 05:45and I just wanted to take a second to talk about ATP synthase that very,
05:45 --> 05:56very last step. And the formation of ATP because it's one of my favorite proteins in biology in order to make ATP this ATP synthase protein will rotate like a
05:56 --> 06:01motor and it's this rotation that allows for the generation of ATP in 1997.
06:01 --> 06:13Some very clever scientists from the Tokyo Institute of Technology actually design an experiment that allowed them to visualize this rotation under a microscope,
06:13 --> 06:17which for me is absolutely amazing and very beautiful.
06:17 --> 06:26So this is one of the most elegant and beautiful molecular machines in our body in my opinion at least and it is found in the mitochondria.
06:26 --> 06:37So overall this powerhouse of the cell is only one example of how mitochondria are very closely linked to our metabolism or the process by which our body builds up
06:37 --> 06:49and breaks down the molecules that make up ourselves so mitochondria can all are also intimately involved in the processes that make other important biological molecules,
06:49 --> 06:54including the nucleotides that make up our DNA and RNA.
06:54 --> 06:59Although mitochondria are known as the powerhouse of the cell.
06:59 --> 07:06They also play a role in other key cellular processes that don't necessarily have to do with metabolism.
07:06 --> 07:13For example, mitochondria are really important for a pop ptosis or programmed cell death.
07:13 --> 07:19A pop ptosis is a very important process that is constantly occuring in our bodies.
07:19 --> 07:23A pop ptosis is really important during development.
07:23 --> 07:29For example, in a developing embryo initially when limbs develop there are cells.
07:29 --> 07:41In between what will eventually become each of the individual fingers and those cells need to undergo this program cell death in order to allow for each of the individual
07:41 --> 07:45fingers to form in adult animals an adult.
07:45 --> 07:55A pop ptosis is important to get rid of any cells that may have gotten damaged in a way that won't damage the other cells around it.
07:55 --> 08:00So during a pop ptosis a group of protein cleaving enzymes essentially fancy.
08:00 --> 08:04Molecular scissors that will chop up any protein around.
08:04 --> 08:14It called caspases are activated an these caspases will begin to systematically breakdown proteins in the cell during apoptosis.
08:14 --> 08:24And healthy cells, these cast spaces are in an inactive form so that they don't digest proteins in the cell inappropriately so they must be activated in order to function
08:24 --> 08:29one of the key proteins required for the activation of caspase is is called cytochrome.
08:29 --> 08:40C cytochrome C is actually part of that electron transport chain that I mentioned previously in the for when the mitochondria is performing its powerhouse of the cell roll.
08:40 --> 08:47So cytochrome C is really important in one of the first steps of a pop ptosis so during apoptosis.
08:47 --> 09:00The outer membrane of the mitochondria will rupture allowing for cytochrome C to be released into the cytoplasm where it can interact with and activate these caspases to allow for
09:00 --> 09:03the progression of a pop ptosis.
09:03 --> 09:14So essentially the mitochondria allows for a physical separation between these caspases and cytochrome C in order to prevent unnecessary cell death.
09:14 --> 09:24Overall, the mitochondria are incredible organelles that are not only important as the powerhouse of the cell but are also involved in many other key cellular processes.
09:24 --> 09:28You've talked a lot about what mitochondria do in ourselves.
09:28 --> 09:38How do mitochondria affect us at the level of the Organism well mitochondria are really important for a lot of things you know they make the energy that we need
09:38 --> 09:40in order to move on things like that.
09:40 --> 09:45But one cool thing that mitochondria does is that it actually helps newborn babies.
09:45 --> 09:49Keep warm through a process called non shivering thermogenesis.
09:49 --> 09:55I previously mentioned that when mitochondria are acting as the powerhouse of the cell.
09:55 --> 10:06The electron transport chain. We use the high-energy molecules created by breakdown of sugar along with oxygen to make a gradient of positively charged hydrogen ions.
10:06 --> 10:12So during non shivering thermogenesis specifically in the Brown adipose tissue of infants.
10:12 --> 10:15There is the protein called uncouple.
10:15 --> 10:26Ng protein that will prevent this positively charged hydrogen ion gradient from being used to make ATP and instead it will be used to generate heat so you said that
10:26 --> 10:36oxygen is required to make the hydrogen ion gradient used to make ATP or heat is non shivering thermogenesis affected if a baby doesn't get enough oxygen.
10:36 --> 10:48Yeah, so babies who don't get enough oxygen can't actually do non shivering thermogenesis so along with all the other side effects that you would have from having low oxygen,
10:48 --> 11:01they can't properly regulate their body temperature so there are chemicals that are capable of performing the same function as uncouple Ng protein performs in the Brown adipose tissue of
11:01 --> 11:15these babies. These molecules are called Uncouplers in 1933 and Uncoupler called 24 dinitrophenyl or DMP was found to cause significant weight loss in adults.
11:15 --> 11:25The rationale behind this drug is that DNP essentially makes it very difficult for your body to build up ATP because DNP is.
11:25 --> 11:28Causing this hydrogen ion gradient.
11:28 --> 11:36That's built inside of your Modoc Andrea to be used to make heat instead of to be used to make ATP so your body has to breakdown.
11:36 --> 11:43A lot more fats and sugars that you can zoom in your diet in order to get the amount of ATP that it needs sense,
11:43 --> 11:47so much of it is being turned into heat.
11:47 --> 11:51So this sounds like a miracle drug and you may be asking yourself.
11:51 --> 11:55Why isn't everybody taking this who has issues with wait?
11:55 --> 11:59Why haven't? Why hasn't this solved obesity in America.
11:59 --> 12:03Unfortunately, this is too good to be true in 1938.
12:03 --> 12:14DNP was labeled as extremely dangerous and not fit for human consumption by the FDA there is a major problem with this drug that you may have picked up on
12:14 --> 12:17since the energy from food is turned into heat.
12:17 --> 12:26Instead of ATP there's an increase in body temperature that can lead to acute toxicity and death as a result of this hyperthermia.
12:26 --> 12:33Is there a Safeway for the young couple hours to be used as a weight loss drug well regardless of?
12:33 --> 12:41What uncoupler you use you're going to get this increase in temperature that's just the fundamentals of how it works,
12:41 --> 12:46so you would have to pick a dose of uncoupler that would allow for A.
12:46 --> 12:54Amount of You know hyperthermia that wouldn't kill you.
12:54 --> 13:00But then you have to ask you know is the amount of weight loss that you get from this low level of the drug.
13:00 --> 13:04Worth it a man also.
13:04 --> 13:11Sense it's very easy to take too many of these drugs.
13:11 --> 13:20To prevent this hyperthermia side effect and so would be very easy for people to take too much of this drug and.
13:20 --> 13:26Have very dire extreme side effects.
13:26 --> 13:31So Emma has covered how mitochondria very important organelles within eukaryotic cells,
13:31 --> 13:37but to make things even more interesting mitochondria were once their own cells separate from your from eukaryotic cells.
13:37 --> 13:45The process by which mitochondria became part of ourselves that we know them now is known as an diesem endosymbiosis.
13:45 --> 13:49Following the discovery that mitochondria had their own DNA in the 1960s,
13:49 --> 13:54the first work theorizing that mitochondria originated separately from the human cells was put forth.
13:54 --> 14:02In 1967, Lynn Margulis proposed that in this proposed the endosymbiotic theory for the integration of mitochondria in human cells.
14:02 --> 14:11The endosymbiotic theory states that mitochondria were early bacterial remnants that were engulfed by early eukaryotic cells around 1 billion years ago,
14:11 --> 14:20so do you know? How long it took scientists to fully accept this theory in her report doctor margolis put forth multiple theories for Endo Symbio.
14:20 --> 14:22Sis and the human cell,
14:22 --> 14:24she stated that maybe eukaryotic flagellum.
14:24 --> 14:29Or Basil bodies of flagella and the mitotic apparatus were also due to endosymbiosis.
14:29 --> 14:33However, not all of her endosymbiotic theories were widely.
14:33 --> 14:36Where is widely accepted as mitochondria?
14:36 --> 14:41Namely, because no genome has been found for the flagella to support this theory.
14:41 --> 14:51Interestingly, the paper in which he first proposed this called on the origin and my toasting cells was said to be rejected by 15 journals before being accepted in the
14:51 --> 15:02Journal theoretical theoretical biology identifying the jeans in mitochondria and plastids is what has allowed the confirmation that these are now included in the eukaryotic cell through endosymbiosis.
15:02 --> 15:06There was significant debate in the 70s and 80s over weather.
15:06 --> 15:09There was an origin from within or origin from,
15:09 --> 15:12without so this means like did did these organelles.
15:12 --> 15:21Origin originate within the cell originate outside of the cell and it appears that in the late 80s and early 90s consensus converged around mitochondria,
15:21 --> 15:33originating outside of the cell and this was especially clear after the full genome was able to be sequenced and we were able to construct phylogenetic trees to prove this.
15:33 --> 15:40So Interestingly there are actually some eukaryotic cells that can function without mitochondria.
15:40 --> 15:45So, although these mitochondria are incredibly important,
15:45 --> 15:50it turns out that it's possible for you carry outs to exist without them.
15:50 --> 15:53In 2012, a group of scientists sequence,
15:53 --> 15:55the whole genome of a protozoa,
15:55 --> 15:59which is a category of single celled eukaryotic cells.
15:59 --> 16:01This part is Oh is called?
16:01 --> 16:14Mono sercombe noise and I apologize to those scientists for my butchering of the name so this Organism belongs to a group of eukaryotes called oxy monads and this group
16:14 --> 16:18of eukaryotes live in the gut of wood eating insects,
16:18 --> 16:24such as termites and a pair appear to play a role in the digestion of wood,
16:24 --> 16:34which is wild so these scientists found that mono circum noise has no trace of any jeans that encode mitochondrial proteins.
16:34 --> 16:42Instead, they identified components that would allow this you carry out to perform anaerobic respiration,
16:42 --> 16:45which is oxygen independent ATP production.
16:45 --> 16:52Additionally, mitochondria are involved in assembling something called iron sulfur clusters,
16:52 --> 16:58which are important in the function of certain proteins within eukaryotic cells.
16:58 --> 17:03And these scientists found that.
17:03 --> 17:16This you carry out has a different system for most eukaryotes to assemble these iron sulfur clusters and that this assembly process more similarly resembles the process found in prokaryotic
17:16 --> 17:19cells such as bacteria, So what about our cells.
17:19 --> 17:23I know red blood cells don't have any don't have a nucleus,
17:23 --> 17:31but do they have mitochondria as Emma has alluded to research on mitochondria has only increased overtime in 2016,
17:31 --> 17:41it surpassed the nucleus? As the organelle with the most medical publications per year of large part of why mitochondria is still so heavily studied with in biology and medicine
17:41 --> 17:47is because mitochondrial DNA is associated with many physiological processes and disease states.
17:47 --> 17:54Certain mitochondrial DNA haplogroups, which are groups of single nucleotide polymorphism are associated with longevity longevity.
17:54 --> 18:00Athletic performance adaptation to high altitude and neurodegenerative disorders like Alzheimer's,
18:00 --> 18:03and Parkinson's, and mask an.
18:03 --> 18:06An macular degeneration to list a few.
18:06 --> 18:09Mitochondrial DNA is discussed in many areas of science,
18:09 --> 18:14partly because it is a line of DNA that is carried their own maternal ancestors.
18:14 --> 18:18We know that we acquired genetic components from both of our parents.
18:18 --> 18:30However, sperm only provides nucleus DNA an not the mitochondrial DNA so the organelles issue technically focused on all organelles where there any other editor picks that you wanted to
18:30 --> 18:35mention? Yeah, so it was actually so when I read through all the papers in this issue.
18:35 --> 18:37It was really a standing to me.
18:37 --> 18:50How large the mitochondria loomed even over manuscripts that weren't about mitochondria so two of my favorite editors picks one of them was about lipid droplets in the management of
18:50 --> 18:53cellular stress and that one was by.
18:53 --> 18:56Eva jargon Tony Peten. Um,
18:56 --> 19:00which I knew I knew nothing about lipid droplets prior to reading.
19:00 --> 19:12This manuscript, but a substantial part of this manuscript actually also focused on mitochondria and how these lipid droplets are interacting with mitochondria to deal with energy storage and the
19:12 --> 19:15amount of data being stored in the cell.
19:15 --> 19:27And then the other manuscript that I really liked was an English mania and they are parasite that gets into your cell and then forms a vacuole in which they
19:27 --> 19:33grow and this manuscript was looking at the proteins that were on this parasite.
19:33 --> 19:38Parasite vacuole membrane and how this is affecting this parasite host interaction,
19:38 --> 19:44which on the face of it doesn't really seem to be about mitochondria and I don't think they actually mentioned them.
19:44 --> 19:47But as someone who also studies and intracellular parasite.
19:47 --> 19:51I thought this was very cool and in my case in Coxiella,
19:51 --> 20:01which is what I study not leishmania mitochondria are incredibly important to the infection process and whether this is able to happen or not because both the parasite and the
20:01 --> 20:04host still need energy so that was another editors pick.
20:04 --> 20:06And then the final editors pick,
20:06 --> 20:11was about localization of a protein into the nucleus,
20:11 --> 20:15which is part of the nucleus where ribosomes are created.
20:15 --> 20:18This one doesn't have a whole lot to do with mitochondria,
20:18 --> 20:20but it was also pretty cool.
20:20 --> 20:27Awesome it's so cool to hear all the wide range of topics that you can have in this issue and it's crazy,
20:27 --> 20:31that so many of them somehow can be related back to the mitochondria.
20:31 --> 20:34Actually, while we're on the topic.
20:34 --> 20:36I have one more. I want to spotlight,
20:36 --> 20:43which was rose at all in this paper as I mentioned mitochondria are not just static little kidney.
20:43 --> 20:50Bean shaped things they have these really complicated networks and they're constantly moving around and doing things.
20:50 --> 20:57And so this one paper by rose at all is looking at the proteins that are required for making this Fusion and vision happen.
20:57 --> 21:04I'm really goes into a lot of detail about those proteins and is also talking about Fusion and vision and chloroplasts,
21:04 --> 21:06which we didn't talk about today,
21:06 --> 21:09so if you're interested in that that's another paper.
21:09 --> 21:12You could read awesome. I as a cell biologist.
21:12 --> 21:18I think that watching mitochondria Fusion and vision is super cool love those microscopy docs.
21:18 --> 21:25So we have one more question for you so why were you interested in working on a Yale Journal Biology.
21:25 --> 21:33In Madison issue that is specific to organelles so I had mentioned that my work is an intracellular bacteria.
21:33 --> 21:40Coxiella and on how it's interacting with the host so that's I really like a lot of Cell Biology,
21:40 --> 21:41a lot of my papers.
21:41 --> 21:49I read in a lot of the things I think about our very much cell biology related even though I am a microbiologist.
21:49 --> 21:57Um and so when we decided we wanted to When would you be on voted that we wanted to do an issue on organelles it was when I was very
21:57 --> 21:58interested in and I mean.
21:58 --> 22:00I also had the spare time to do it,
22:00 --> 22:02so that was how I ended up on this issue,
22:02 --> 22:07so thank you for joining us and for walking us through your issue and thank you.
22:07 --> 22:12Mo for contributing your great followed biology background to this special episode.
22:12 --> 22:19There are many other people behind this podcast that you might never get a chance to hear so we like to thank the Yale school.
22:19 --> 22:21medicine from being our home for YJBM,
22:21 --> 22:24the podcast. We like to thank the Yale broadcast.
22:24 --> 22:29Center for hope with recording editing and publishing are podcasts shout out to Ryan McEvoy.
22:29 --> 22:31Thank you to the YJBM editor board,
22:31 --> 22:33especially our editor in chief,
22:33 --> 22:39which is also Amelia Hallworth and that also includes Devon Washe in deputy editors for the organelles issue,
22:39 --> 22:42which were Amelia Hallworth and John Ventura.
22:42 --> 22:48Finally, thanks to you. Our viewers for turning into for tuning into this episode of the YJBM podcast.
22:48 --> 22:54We love your feedback and questions so feel free to tell us your thoughts and by emailing us at YJBM at yale.edu.
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Information

As you may have heard, mitochondria is the powerhouse of the cell! This is a phrase commonly mentioned in introductory biology textbooks and reiterated throughout our lives in an effort to prove that we do, in fact, remember something from high school biology. The first published manuscript to announce this was written by Dr. Philip Siekevitz and published in the Scientific American in 1957. It’s a short review with multiple images taken an electron microscope to confirm Dr. Siekevitz statement that the mitochondria’s form mirrors its function. However, research on mitochondria began almost exactly a century before this powerhouse statement was made...

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