Autophagy Macroautophagy Importance in Health. Hey, everyone, in this I’m going to talk to you guys about macro autophagy, and more specifically, talk to you guys about what macro autophagy is. What are the steps involved in macro autophagy? Why macro topic is important. And I’ll also talk about some of the regulation of macro autophagy and some drugs that we use to actually activate or inhibit macro autophagy. So to begin, what is autophagy?
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Autophagy is a key lysosomal degradation pathway that helps maintain cellular homeostasis and performs important functions in the immune system, among other things. Recent studies suggest that autophagy may play a role in human health, and it is becoming increasingly evident that this process is important for maintaining overall cellular health. Here, we will explore the importance of autophagy in health and discuss some of the ways it can be beneficial.
Autophagy Macroautophagy Importance in Health
Autophagy Macroautophagy Importance in Health Well, autophagy if you break it down. Auto means self and Fagi means eating, so it’s a process of self eating. And now autophagy is one of two major protein degradation systems in pretty much all forms of life, fungi, plant, and animals, the other system being the proteosomal degradation pathway. Now there are actually three types of autophagy in mammalian cells. The first one is the one I’m going to talk to you guys about in this video, macro autophagy, and that is simply the bulk degradation of different cellular components via autophagosomes.
The other types of autophagy in mammalian cells include microautophagy and chaperomedia autophagy. And I’ll talk to you guys about those types of autophagy in another video. Nevertheless, all types of autophagy have one thing in common, and that is the degradation of substrates within the lysosome, whether those substrates be proteins, lipid droplets, or organelles. Now, because it is a process of degradation, autophagy is responsible for cellular waste clearance. So that means it recycles nutrients, subunits such as amino acids.
importance of autophagy
And because of this, it is critically important in homeostasis. And another related process known as autophagic. Cell death can occur as well through autophagy. And because of all these things, because it’s involved in homeostasis and because it’s involved in a process known as autovagic, cell death is a critical process during disease. So it’s critically important to know about autophagy and what it’s doing.
Autophagy Macroautophagy Importance in Health So this topic of this video is macro autophagy, and I want to just specify to you guys that macro autophagy is an umbrella term for various different types of autophagy that all utilize autophagosomes and are degraded through bulk degradation in the lysosome. And different types of macro autophagy are named according to what they actually degrade. Now, one type of macro autophagy is mitophagy, or the bulk degradation of mitochondria. Another type of macrotophagy is reticulophagy, or the degradation of the endoplasm reticulum in the lysosome. Another one is nucleophagy, the degradation of nucleus in the lysosome.
autophagy function
And you can see all these are related to organelles degradation. Another type of macrotophagy is lipophagy, or the degradation of lipid droplets. And another type of macrotopy is actually called xenophagy, which is the degradation of foreign microorganisms such as bacteria. And this is actually not all the different types of macrotops. There are many different types of microbiology.
Autophagy Macroautophagy Importance in Health I just want you guys to know that this is an umbrella term for many different processes. And each type of macrotophagy is named by the type of substrate that it’s targeting.
But even though they’re all degrading, different types of substrates, they all use a similar process. And this is what I’ll show you here. So all types of macro autopsy begin at the endoplasmic reticulum and it starts by the formation of something called an Omega zone or a preautophagosome budding of membrane off of the endoplasma reticulum. And this preautophagosome, it’s a developing cup shaped membrane and it requires a protein complex with proteins ATG just stands for autophagyrelated gene or autophagy protein. So ATG 13, it requires Fib 200 and ATG 101.
autophagy pathway review
Now, you don’t need to know all these proteins for now, I just want you guys to know that Oak one is important for initiating processes of pre autophagosome formation and initiating steps of macrotophagy. So the next step that occurs as this preauto phagosome is becoming larger and becoming more elongated, there’s another protein complex that gets involved in this protein complex involves vascular protein sorting 34, bps 34, bps 15, and Beckyn one proteins. Now, Oak one actually activates Beklin one through phosphorylation. And this complex with VPs 34, VPs 15, and Becklin one all act like a class three Pi three kinase. And they actually produce Pip three from Pip two.
Now, this increasing concentration of Pip three actually leads to the recruitment of these things we call WIPI proteins or WIPI proteins to the pre autophagosomal membrane. Now, once those Whippy proteins have been recruited, other proteins are recruited as well. Some of these proteins include P 62, which is ubiquitous cargo binding protein MBR. One is a related protein that acts similarly to P 62. And these act as somewhat partial selective receptors for different substrates in the cell.
when does autophagy occur
Now, another protein that’s very important in this process as the preautophagosome elongates and matures and becomes larger is something called LC three one. So another protein complex that’s important in this process as well is the protein complex that consists of ATG five, ATG 16 and ATG twelve. And this complex actually helps to target particular substrates and particular proteins to the developing autophagy zone. Now, LC three one is crucially important in all this process. Now, LC 31 actually comes from LC three or pro LC three, they call it and pro LC three is actually cleaved by assisting protease ATG four into LC 31.
So once LC 31 has been targeted to the autophagosomal membrane, it actually gets activated by ATG seven and bound to ATG three and then actually conjugated to PE or fossil ethanolamine to actually form LC 32. So as this conversion from LC 31 to LC three two occurs, the autophagosome actually continues to elongate it and actually becomes a full fledged autophagosome vesicle. This is when we call it a mature autophagosome. And then once you have a mature autofagosome with its contents, it’ll actually fuse to the lysosome via Snare proteins and Rab seven.
lc3 p62 autophagy
Once it fuses to the lysosome, it becomes an autolysosome. And then what happens is the membranes fuse together. The autofagosome releases its contents into the lysosome and then those substrates are actually degraded in the acidic lysosome by particular proteases such as cathepsin B and L. There are other cathepsin as well. Now, because this is a very complicated process, there have been methods to actually categorize each part of this process.
The first process is typically referred to as initiation, the second process whereby we’re having formation of Pip. Three, this is what we call nucleation, another process. As the autofagazone actually becomes larger through LC 31 conjugation processes. This is what we call elongation. Then once the actual autofagainsimal vesicle actually forms and closes, this is what we call maturation.
And then the final step is fusion. So this is kind of how we categorize each of these processes or steps in macro autophagy. So because this process is very important, there are many different types of regulation of the pathway. One of them is through AMPK or Ampe activated protein kinase, which activates ol one. Another one is through mTOR, which I’ve shown you guys in the previous video that it actually inhibits olk one.
