Autophagy pathway, longer than you think

2018-06-27 09:22:34 GMT+0800

The word autophagy comes from the Greek word auto-, meaning "own", -phagein, which means "eat." To put it plainly, cells eat themselves. This concept was first proposed in the 1960s, and Yoshinori Ohsumi, a Japanese scientist, was one of the best performers in this field. In 2016, he won the Nobel Prize for medicine for his research on the mechanism of autophagy.

In the literature, autophagy is a highly evolutionarily conserved eukaryotic cell used to degrade and recycle intracellular biological macromolecules and damaged organelles. The completion of autophagy depends on the lysosomal function and is closely related to the body's various physiological and pathological processes: tumor, immune, and nervous system diseases.


Under certain circumstances, some molecules inside and outside the cell will initiate autophagy, followed by a cardiac course of cascade signaling of autophagy. At present, at least 20 or more protein molecules are known. As a researcher, on this road, you have detected several points. What is the effect?

Autophagic signaling pathway


1. Open the key to autophagy: mTOR

mTOR is a serine/threonine kinase that regulates cell cycle, growth and proliferation. mTOR regulates the activity of the autophagy initiator Atg1/ULK1 through autophosphorylation and controls autophagy.

Antibody source:anti-MTOR antibody



2. Autophagic lock: ULK1


ULK1 activates and phosphorylates mAtg13, FIP200, and ULK1 itself, thereby opening the first step in autophagy; in the absence of nutrients, AMPK can also activate its activity by phosphorylating ULK1, thereby further promotingautophagy.

Antibody source:anti-ULK1 antibody


3. Super protein complex Atg5-Atg12-Atg16, even up to 800 kD


Atg16 binds to Atg12-Atg5 when autophagy occurs. Atg16 contains a helix coiled structure that tends to form oligomers, making it possible to link more Atg12-Atg5 to form a huge complex. When autophagy occurs, this complex is localized on the membrane and participates in the formation of LC3-II.

Antibody source:anti-ATG5 antibody


4. Detection of autophagy occurred in the game: LC3


At the time of autophagy, LC3-I uniformly distributed in the cytoplasm forms LC3-II with membrane-binding ability with the help of Atg7/Atg5-Atg12-Atg16.

Antibody source:anti-LC3B-Specific antibody


OK.

Take the main road for a walk today.

Next time, let's explore the path to autophagy.

Note: All test images are chosen from the literature, please refer to the reference for details.


Reference

1. Mehrpour M, Botti J, Codogno P. Mechanisms and regulation of autophagy in mammalian cells[J]. 2012.

2. Fang Mengdie, Liu Bo, Liu Wei. Progress in molecular and cellular mechanisms of autophagy [D]., 2012.

3. Pengo N, Agrotis A, Prak K, et al. A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B[J]. Nature Communications, 2017, 8(1): 294.

4. Elkis Y, Cohen M, Yaffe E, et al. A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells[J]. Nature communications, 2017, 8(1): 940.

5. Cottam E M, Maier H J, Manifava M, et al. Coronavirus nsp6 proteins generate autophagosomes from the endoplasmic reticulum via an omegasome intermediate[J]. Autophagy, 2011, 7(11): 1335-1347.

6. Kochetkova E Y, Blinova G I, Bystrova O A, et al. Targeted elimination of senescent Ras-transformed cells by suppression of MEK/ERK pathway[J]. Aging (Albany NY), 2017, 9(11): 2352.

7. Wold M S, Lim J, Lachance V, et al. ULK1-mediated phosphorylation of ATG14 promotes autophagy and is impaired in Huntington’s disease models[J]. Molecular neurodegeneration, 2016, 11(1): 76.

8. Yuan J, Zhao X, Hu Y, et al. Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway[J]. International journal of molecular medicine, 2018, 41(4): 2086-2098.

9. Zhang J, Bai Y, Huang L, et al. Protective effect of autophagy on human retinal pigment epithelial cells against lipofuscin fluorophore A2E: implications for age-related macular degeneration[J]. Cell death & disease, 2015, 6(11): e1972.