Last year's Nobel Prize in Physiology or Medicine was awarded to the Japanese National People's Congress Yu Liangdian. Who is this? This is a well-known person in the industry. The reason why he was awarded the prize was that he discovered the mechanism of autophagy. Everyone knows about cells. What exactly is autophagy? Let's do it together.

Yoshinori ohsumi studied the autophagy mechanism of Saccharomyces cerevisiae. Saccharomyces cerevisiae is a model organism, which is very classic. After more than 20 years of research, 34 genes related to autophagy were found in yeast. What is autophagy?

In fact, autophagy is eating yourself. Just don't eat with your mouth. After all, cells have no mouths. Autophagy is that cells degrade their own structures, disassemble some temporarily useless parts into the smallest modules, and then reassemble them into what they need. This is autophagy.

In plant cells and yeast cells, autophagy occurs in vacuoles. Autophagy occurs in lysosomes of animal cells. From a protein to the whole organelle, it is degradable. Of course, these things are all made up of amino acids.

Autophagy is a pathway of intracellular catabolism. There is another way, called ubiquitin proteasome pathway. Simply put, it is to add ubiquitin to protein, mark it, and then send it to proteasome for digestion.

The history of autophagy discovery is like this.

First of all, in 1956, Clark found something with a membrane structure in the kidney cells of mice with electron microscope. This kind of thing is quite substantial, and the cytoplasm contains many things, even mitochondria.

Then, in 1963, a lysosome meeting was held. Christian Renede Duve first called this thing autophagy.

In 1990s, Daniel J.Klionsky and yoshinori ohsumi (yoshinori ohsumi) began to study autophagy with yeast.

Later, more and more scientists joined the team studying autophagy.

Autophagy can be divided into three ways. This is divided according to how to package materials and how to transport them.

The first one is called macro autophagy, also called macro autophagy, which is relatively large as its name implies. Cell membranes or other double-layer membranes are used to wrap unwanted things and then fuse with lysosomes. This is usually a relatively large organelle or something.

The second is called autophagy. As the name implies, it is relatively small, that is, lysosomes or vacuoles directly use themselves to devour those things that need to be degraded. Maybe it's an organelle, maybe it's protein.

The third type is called molecular chaperone-mediated autophagy. This means that the molecular chaperone restores the protein in the cell from the folded state to the unfolded state, and then puts it into lysosomes.

These three autophagies are all autophagy ways. The first one is the most important and thoroughly studied. So in a narrow sense, autophagy is autophagy.

In addition, autophagy is divided into two types, non-selective autophagy and selective autophagy. In yeast, selective autophagy can be divided into cvt pathway, mitochondrial autophagy and peroxisome autophagy. The first meaning is amino skin enzyme, glycopyrrolate.

Precursors of glucanase and other enzymes are sent to vacuoles, which activate these enzymes and then send them back to cytoplasm, thus playing the role of hydrolase.

There is only the first type in yeast cells, autophagy.

Autophagy happens like this.

In the first step, the nucleus signals that a certain part of the cell needs to be degraded, or garbage induces a certain reaction in the cell, so autophagy occurs. After these signals are accepted by the cells, autophagy is formed in yeast cells near a protein called Atg8, also called PAS. Mammalian cells begin to form a flat, bowl-shaped double-layer membrane structure somewhere where endoplasmic reticulum and mitochondria contact. This structure continues to expand and eventually becomes autophagy. This kind of membrane may be a part of some organelle membranes, which is used to wrap things to be degraded, such as endoplasmic reticulum, Golgi apparatus, endocytosis, plasma membrane and mitochondria. Of course, it can also be assembled into a film immediately in situ. Wrap up those unnecessary things. This step is autophagy. This is temporary.

In the second step, autophagy gradually expands, closes and wraps the garbage. Autophagy is spherical.

The third step is the fusion of autophagy with vacuoles or lysosomes. Anyway, they are all membranes, and there is no pressure to fuse together.

The fourth and final step is that after autophagy is fused with vacuoles or lysosomes, those unnecessary things are decomposed under the action of some enzymes. Decomposition into amino acids, fatty acids, etc., and the remaining residues are discharged from the cells. Of course, it is also possible to keep it temporarily. Maybe it can be recycled.

Speaking of autophagy, you must think of another word. Apoptosis. So are these two the same thing?

The answer isno. Autophagy and apoptosis are not the same thing. Are they related? This must be available.

There are three kinds of cell death: necrosis, apoptosis and autophagy. Autophagy and apoptosis go hand in hand.

Necrosis refers to the damage of the body, the cessation of cell metabolism and the loss of function. Lysosomes release hydrolases to decompose the whole cell, or white blood cells travel all the way to release hydrolases.

Apoptosis is also called 1 programmed cell death. It depends on a large number of hydrolases, such as caspase. Apoptosis has the following characteristics: chromosome concentration, cell shrinkage, DNA degradation and apoptotic body formation. This is from the high school biology book. Finally, the rest is eaten by macrophages.

Autophagy is also called programmed cell death type 2. This is purely lysosome. Does not depend on certain enzymes.

What is the relationship between apoptosis and autophagy? Apoptosis and autophagy are a dynamic balance. Autophagy may precede apoptosis, thus initiating apoptosis. Autophagy may also inhibit apoptosis, thus protecting cells. Autophagy may also be transformed into apoptosis.

In these three steps, autophagy is completed. But there is a problem. Where did the film that originally wrapped the garbage come from?

In yeast, this process is like this. The membrane will expand and grow at the autophagy assembly site (PAS, near vacuole) under the action of Atg8 and other proteins. Then it developed into autophagy.

This process is different in mammalian cells. The autophagy-forming regions are all over the cell. So now we have a lot of assumptions.

The first hypothesis holds that autophagy membrane comes from endoplasmic reticulum. Autophagy is formed where endoplasmic reticulum and mitochondria contact. Therefore, it has always been said that autophagy membrane comes from mitochondrial outer membrane.

There are also three hypotheses that autophagy membrane comes from Golgi apparatus, endocytosis (that is, from cell membrane) and cell membrane. Each of these hypotheses has its own evidence, and it is hard to say which one is right at present. Maybe it doesn't matter. Nobody knows.

Autophagy is such a thing. You probably understand, right? Autophagy is a very conservative process in cells and rarely evolves. Autophagy appears to adapt to the environment, especially in bad years, such as lack of nutrition, hunger, great pressure, or special lack of oxygen and water, so autophagy is needed.

Autophagy is now very important for clinical research. For example, tumors can often grow in very harsh environments because autophagy of tumor cells is very strong. So theoretically, if autophagy of tumor cells is blocked, will it not grow?

Another example is some neurodegenerative diseases, such as Parkinson's disease, in which there are some misfolded protein in the brain. And it can't be removed. It is also a problem of autophagy in essence.

Autophagy is also related to immunity. In a word, the research on autophagy is not deep enough at present, especially on autophagy genes and autophagy mechanisms. So, let's wait for scientists to try again ~