Mitochondria: ATP Production and Apoptosis

by Richard Mitchell, MD, PhD

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    00:01 Alright, then. Let's go on and we'll hit on another topic that's very important, obviously, for maintaining subcellular organization, and that's generating ATP, adenosine triphosphate.

    00:14 That's the currency by which the cell runs.

    00:16 So, let's talk about energy, and we'll talk about mitochondria, but also, it's important, really important, that you realize it's not just about making ATP.

    00:25 That little organelle, boy, it does a lot of other really cool stuff too.

    00:29 Okay, so here we go. So, as you can see in the title, Mitochondria: More than Just ATP.

    00:36 So, we have certain structures of the mitochondria.

    00:38 We have the outer membrane, there's an inner membrane, and inner membrane is actually where the electron transport is occurring, and that's where we're moving protons from inside to outside that when they go back into the inside, that's when we generate ATP.

    00:56 That's the chemiosmotic principle developed by Dr. Peter Mitchell, no relation.

    01:01 Okay. We have cristae. Those are the folds of the inner membrane, giving it structure and making it very recognizable when we see them by electron microscopy.

    01:10 We have the space in between and that's where the protons are pumped when we are moving electrons down the transport chain in the inner membrane.

    01:20 We have the matrix, and this is where the major metabolic enzymes reside.

    01:24 So, there will be a number of metabolic diseases that occur because of defects in that location.

    01:31 And then, we have various granules, that these are particles within the mitochondria that we can identify.

    01:36 These are aggregated proteins and other protein complexes.

    01:40 We have ribosomes and circularized DNA.

    01:43 It's important to recognize that mitochondria also synthesize a subset of the proteins that are contained within them.

    01:52 And this has certain ramifications, but it's also an interesting reflection of where do these little guys come from in the first place.

    02:00 Okay, so we've named the players. Let's talk more about mitochondria.

    02:04 So, they evolve from prokaryotes.

    02:09 They were -- a long time ago, billions of years ago, they were taken up.

    02:15 These were little bacteria-like prokaryotes that got taken up into a eukaryotic cell and set up a mutual admiration society.

    02:28 And they got a home, but they also provided energy for the eukaryote that had taken them up.

    02:34 So, they're evolved from prokaryotes.

    02:36 So, that means, in fact, they used to be, honest to god, free-living bacteria.

    02:44 They had their own circularized DNA and some of that has been retained.

    02:50 It -- over time, more and more of the DNA has been exported and now incorporated into the host genome.

    02:57 About 1% of the total DNA content in any given cell is from mitochondria.

    03:04 They also have all their very own set of transfer RNAs.

    03:09 So, they can make their own proteins.

    03:12 They transcribe and they translate like bacteria.

    03:16 This will come back to be an important point in a few talks from now, but we'll revisit that point.

    03:23 What do I mean by that? It means that as they transcribe, as the mitochondria transcribe their own little subset of proteins that they do, they start off with informal methionine. That's what bacteria do.

    03:37 They put informal methionine.

    03:39 It's the first amino acid on every protein they synthesize.

    03:42 Same thing with mitochondria.

    03:45 They put informal methionine on there.

    03:48 So, in many ways, they look like a bacteria.

    03:51 They also is part of that transcriptional machinery.

    03:57 They are susceptible to the same antibiotics that bacteria are susceptible to.

    04:05 So, the machinery is also very similar.

    04:07 Okay, so importantly, they generate ATP via the proton electrochemical gradient that we talked about very briefly.

    04:15 And I'm not gonna go into any of those details.

    04:17 I'm really gonna focus more on these other issues associated with the mitochondria.

    04:22 Okay, so ATP, fine. They are also source of all the metabolic building blocks.

    04:29 So, they're gonna be making the intermediates, the glucose, and the amino acid intermediates, and many of the lipid intermediates that are gonna be important for putting together other cellular components.

    04:40 So, the matrix is really important in this.

    04:43 They are maternally inherited.

    04:46 So, you get your mitochondria from mom's oocyte, from her egg.

    04:51 You get, basically, none from dad at all.

    04:55 So, it's a way of also following lineages by looking at the maternal -- the infant transport.

    05:04 There are over a thousand, 1,098 proteins that constitute a mitochondria.

    05:11 13 of those are ones that are actually synthesized by the mitochondria.

    05:19 And therefore, maternally inherited.

    05:21 The other 1,085 proteins actually come from the nucleus and are imported into the mitochondria. Pretty cool.

    05:34 We'll talk in a subsequent topic discussion about how that can happen.

    05:40 All right, they, on average, have a 10-day turnover.

    05:44 So, they last for 10 days and then we start over again.

    05:47 In fact, if you don't do that, they become progressively less adept at making ATP and they make more oxygen free radical intermediates that are incredibly damaging to the cell.

    05:59 So, if you don't constantly turn them over, they get defective.

    06:02 And when they get defective, they can kill a cell.

    06:05 So, it -- they are also dynamic structures.

    06:07 They fuse with each other, they fragment, they form big mitochondria, they form little, tiny fragments.

    06:15 So, it's a really interesting organelle.

    06:18 And as we're gonna see on the next slide, they're integral to apoptosis.

    06:21 So, that mechanism of cellular suicide is regulated, in many respects, by the mitochondria.

    06:30 So, this little organelle, of which there are about 1,500 per cell on average, does a lot more than just generate ATP.

    06:37 So, how is it involved in apoptosis? We'll come back to this when we talk about cell death in greater detail, so stay tuned.

    06:46 But within the matrix, there is a protein called cytochrome C.

    06:51 And actually, it's not even in the matrix, it's in the inner membrane.

    06:54 It's part of the electron transport chain.

    06:57 When cytochrome C escapes from that location and gets into the cytosol because the mitochondria is damaged or because it specifically released it, that cytochrome C is the nucleus for forming the apoptosome.

    07:12 This is the seven-spoked wheel of death that you see there on the left-hand side.

    07:17 And the cytochrome C is highlighted in that circle black area on each arm of the seven arms of the apoptosome, and that's how we start apoptosis.

    07:27 That will lead to the cell committing suicide.

    07:31 There are many steps, we're not gonna cover those today, but stay tuned because it's really cool.

    07:36 And so, the cytochrome C coming from the mitochondria will tell a cell whether or not to die. Very interesting.

    About the Lecture

    The lecture Mitochondria: ATP Production and Apoptosis by Richard Mitchell, MD, PhD is from the course Cellular Housekeeping Functions.

    Included Quiz Questions

    1. Release of cytochrome C into the cytosol
    2. Mitochondrial swelling
    3. Inactivation of the electron transport chain
    4. Loss of the mitochondrial membrane potential
    5. Loss of cristae in the inner membrane
    1. Transcription initiation with N-formylmethionine
    2. The double helical structure of nucleic acid
    3. Generation of ATP through photosynthesis
    4. The presence of a cell wall
    5. The presence of a membrane-enclosed nucleus
    1. It is maternally inherited.
    2. It encodes most of the mitochondrial proteins.
    3. It is packaged into a dense material called chromatin.
    4. It is dynamic and can fuse with DNA from other mitochondria.
    5. It is required to activate apoptosomes.
    1. At the inner mitochondrial membrane
    2. In the apoptosome
    3. In the cytosol
    4. In the mitochondrial matrix
    5. In the mitochondrial granules

    Author of lecture Mitochondria: ATP Production and Apoptosis

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

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