Apoptosis: Programmed Cell Death

We've touched on apoptosis before, especially when we learned about cancer in the biochemistry series. But let's a closer look. We know that apoptosis is programmed cell death, a failsafe mechanism whereby faulty cells that pose a threat to an organism can be systematically destroyed. How does this work? Where do the signals come from and how do they propagate? What kinds of proteins are involved in carrying out this activity? Come and see!

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[lila]

I made a transcript of the video for a class so I thought I'd go and share it here if anyone was curious and wanted it for whatever reason.
Here it is:


Starting at 0:27
Apoptosis: this is a method by which faulty cells that pose a threat to an organism will undergo self-destruction, essentially programmed cell death, and this is precisely why mutations in genes the code for enzymes that regulate apoptosis are an extremely common cancer. If enzymes can’t carry out self-destruction, a cell will proliferate until a tumor forms. Given the importance of apoptosis to any complex biological system, let’s take a closer look and see how this works on the molecular level. In the most basic sense, apoptosis involved cellular agents chipping up everything within the cell. All the DNA, all the organelles, everything becomes fragmented, and the cell itself shrinks the form lobes, which pinch off and are then digested by specialized cells called scavenger cells. This is important because if a dying cell simply leaked its components totally intact, such as its enzymes, these could potentially be incorporated into other cells and initiate the same faulty mechanisms in those. So everything must be destroyed. In order to understand exactly how this all happened, let’s examine the two ways in which apoptosis can be initiated. Signals can come either from outside of the cell or inside of the cells. If outside, nearby cells release signaling molecules that initiate signal transduction that results in the expression of genes whose protein products carry out apoptosis. Alternately, if the DNA within a cell becomes damaged beyond repair, a series of protein-protein interactions can act as a signal that triggers apoptosis. Let's get a closer look at these signaling pathways. This is a nematode named C. elegans. It’s basically a small worm, so small in fact that it’s made of only about one thousand cells. Because there are so few cells, researchers can more easily trace the ancestry of any given cell, from embryonic development onwards, and it is the case that apoptosis occurs at specific times during the natural development of the organism. In this particular organism, there are two important genes which encode proteins that are essential for apoptosis. These genes are called ced-3 and ced-4, which stand for “cell death”. The proteins they code for have corresponding names, Ced-3 and Ced-4, with a capital C. These proteins are present in all the cells, but in an inactive form. In addition, the gene ced-9 produces the protein Ced-9, which sits in the outer mitochondrial membrane, and acts as a brake that regulates apoptosis. If the signal to undergo apoptosis is received by the cell, signal transduction results in a conformational change in Ced-9 that renders it unable to halt apoptosis, in turn resulting in the production of proteases and nucleases, which are enzymes that chop proteins and DNA. These proteases are called caspases, and the main one in C. elegans is the Ced-3 protein we mentioned earlier. In humans, things are a bit more complicated, with many more different caspases involved, utilizing different pathways depending on the cell type and the signal received. Oftentimes, an external signal results in mitochondrial proteins forming small pores in the outer membrane, such that other proteins within the mitochondria are released, which in turn promote apoptosis. Some of these components have totally different functions within the cell, such as cytochrome c, which is part of the electron transport chain but outside the mitochondrial matrix, it acts as an apoptotic factor. Other times, an internal signal from the nucleus is received, if DNA damage is considerable, or from the endoplasmic reticulum, if protein misfolding occurs. But as we said, while apoptosis is sometimes the last resort for a misbehaving cell, it is often an essential aspect of organismal development. This occurs to varying degrees with different vertebrates to produce hands, feet, paws, and other such limbs. It is required for normal development of the nervous system. And the fact that this process occurs in most eukaryotic life, even single-celled yeasts, demonstrates that this basic mechanism evolved very early in eukaryotic development. Problems with this mechanism lead to a variety of degenerative diseases, such as Alzheimer's disease and Parkinson's disease. Protein aggregation can activate an enzyme that triggers apoptosis, resulting in the death of neurons and loss of brain function. And once again, as we said, when apoptosis is supposed to occur but is unable, due to mutation in genes that code for these apoptotic enzymes, cancer is a probable outcome. So that’s a basic introduction to apoptosis.

[philippefrit]

Hello, nice overview. Just one thing: the proteases are called "caspases", not "capsases".

[Genjoyer]

Thanks Dave! I'm starting my undergrad this summer and I'm majoring in biology, and organic chemistry. Your videos are really helping me feel more confident going in, and I really appreciate your hard work.

[albertchen]

This feel magical, I have been watching your video since high school, college. Now I am in dental school, and I still coming back to you. By the way, keep up the good work, in this 6 min, you are more articulate and precise than my professor.

[tlwwithornament]

Im seeing your subs go up what seems like a thousand every other day or so. Keep it up my man, great content.

[taylorbarnett]

Love you and your work!! I can’t wait to study physics this fall with your help

[SaraeRaveen]

I learned about Apoptosis in Cell Biology & Immunology! I love learning about this stuff!

[hajiqasim]

Dave, your videos help me in exam but what about Necrosis?

[eva]

Caspases, not capsases; great video anyhow!!!

[ricardowilkins]

Replenishing our bodies with stabilized ROS/RNS is one of the most effective methods to assisting the body with efficient programmed cell death. They have several roles in the body, one being cellular messengers and our bodies built-in method to detect repair or replace damaged cells.

[goodyKoeln]

Does it kick in right after the warranty ends?

[Swolhippie]

I appreciate you for making it so easy and fun to learn this. How cool!!

[johnathanabrams]

How does apoptosis work for contractured muscle sarcomeres aka myofascial trigger points?

[drewdurant]

Apoptosis is the most interesting thing ever!

[elozJ]

Thanks Dave for this video. Very helpful..

[sharon]

Exactly before the test! Thank youuuu 🙏🏻

[BloxmasterTimmieh]

Searched up Perfect Cell’s death and I got this, factually though keep up the great work!

[LordDavidVader]

I'll be the first to admit I don't know a lot of details on how you tube advertising works but seeing an add on this for a Nature Works Best cancer clinic seems wrong.

[MarcelinoDeseo]

So faster rate of apoptosis of bone cells lead to osteoporosis?

[hajiqasim]

Simple, super but what about Necrosis?