Year: 2020
Type: dissertation
Abstract: Chaperone-mediated autophagy (CMA) is a mechanism by which individual proteins are selectively bound to chaperones to be translocated across and degraded in the lysosome.We have previously reported that long-lived mouse models have been known to have constitutive upregulation of CMA and also increased AKT phosphorylation.GFAP is one of the only known regulators of chaperone-mediated autophagy, which itself is regulated by AKT.We have found that inhibiting the Insulin/PI3K/AKT pathway by using PI3K inhibitors and PDK-1 inhibitors decreases both AKT and subsequent GFAP phosphorylation in vitro and in vivo.We confirmed that this pathway stimulates chaperone-mediated autophagy independently of other autophagic pathways such as macroautophagy.Lastly, we also report that AMPK has been found to play a role of regulating CMA via the Insulin/PI3K/AKT pathway by phosphorylating IRS-1.
Author: Zachary Ziemba
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3090767085