Question

How might the status of AKT activation impact the synthesis of autophagosomes?

Answer 1

Answer-

According to the given question-

AKT or  serine threonine Protein kinase or protein kinase B or PKB involved in regulation of survival of cell, progression of cell cycle , organization of cytoskeleton , function of platelets, as well as in transport of glucose.

The deregulation of AKT responsible for several diseases such as glucose intolerance,, cancers, autoimmune diseases, schizophrenia, as well as viral infections.

Pathway known as phosphoinositide 3-kinase –AKT–mTOR (mammalian target of rapamycin) responsible for regulation of autophagy , anti-apoptotic signaling, as well as ubiquitin-proteasomal system.

AKT signaling in mammalian cells links with protein degradation pathways

• Ubiquitin–proteasome system - regulate AKT signaling by
  • K63-linked ubiquitination - responsible for promoting oncogenic activation of AKT
  • K48-linked ubiquitination - responsible for proteasomal degradation of phosphorylated AKT
• Autophagy - in mammalian cells it is used for intracellular protein recycling and also for gross disposal or proteins. AKT responsible for phosphorylation of several important molecules which are required for regulation of autophagy. autophagy is induced with the help of AKT–Phafin2 complex which localize the Lysosome.

wortmannin or 3-MA work as  PI3K inhibitors which are responsible for inhibiting autophagy while rapamycin induces autophagy by inhibiting mTORC1. mTORC1 work as  traffic nutrient transporter, responsible for giving signal to Beclin1 and ULK1/ULK2 complexes which is responsible for promoting formation of autophagosome. mTORC1 ubiquitination is required  TRAF6-K63-complex which are responsible for translocation of mTORC1  to Lysosome which activates autophagy.

Along with mTORC1 the AKT is also regulates autophagy because a protein called  Casein kinase II, present upstream of AKT phosphorylates p62 and localizes it to the Golgi body or to the Lysosome, and also  promote clearance of ubiquitinated proteins by autophagy.

Several other such as Beclin1 or ATG, ULK1 or ATG1, and 6FOXO3 also control the process of autophagy.

AKT–Phafin2 as well as p62–TRAF6–mTORC1 complex translocation is required to the site of Lysosome for autophagy which signifies that the complex AKT–mTOR is required for regulation of autophagy.