Question

Describe the main steps in autophagosome formation, outlining the key protein(s) and/or protein complexes involved. What do you think is the role of autophagy in cancer (use example to back up your argument)

Answer 1

Autophagy is a unique membrane trafficking process, in this a newly formed membrane inside cytoplasm called phagophore engulfs, parts of cytoplasm, leading to the production of autophagosome a Double-membraned structure of 400-900nm diameter. Gradually autophagososmes go near the lysosome and attaches with the lysosomal membrane and get degraded. It is a catabolic pathway, linked to various pathological and physiological processes like development, programmed cell death, cancer etc.

The steps of autophagosome formation.

Atg protein is the main protein ,it requires other proteins, for formation of autophagosomes.

Process of autophagy starts with the formation of the phagophore, it is mediated by the class III PI3-K complex, it includes Vps34, Vps15, Atg14 and beclin 1, it progresses by various steps these steps are : (I)Elongation of the phagophore and engulfment of cytoplasmic material targeted for degradation, (II) Formation of the autophagosome, occurs with de-lipidation of LC3-II by Atg4, (III) Fusion of the autophagosome with the lysosome to form the autolysosome, (IV) Degradation of the vesicle content occurs by lysosomal hydrolases and (V) Recycling of the degradaded products (amino acids, lipids and sugars) occurs to produce ATP .

The role of autophagy in cancer:- Autophagy is a survival-promoting pathway in this it captures, degrades, and recycles intracellular proteins and organelles in lysosomes. Autophagy helps in preserveing organelle function, also helps in preventing the toxic buildup of cellular waste products, and gives substrates to carry on metabolism at the time of starvation. Though in some cases autophagy suppresses tumorigenesis, but in most cases it supports or aggravates tumorigenesis. Mechanisms by which autophagy promotes cancer is by suppressing induction of the p53 tumor suppressor protein and maintaining metabolic function of mitochondria.

Examples of Autophagy as tumor promoter are in basal autophagy is upregulated in hypoxic tumor regions, where it is essential for tumor cell survival. Autophagy is also upregulated in RAS-transformed cancer cells and promotes their growth, survival, tumorigenesis, invasion, and metastasis.