Esperanza Arias-Perez
Showed that mTORC2, working with PHLPP1 and Akt at the lysosome, regulates chaperone-mediated autophagy
Associate Professor, Department of Medicine (Hepatology) and Department of Pathology, Albert Einstein College of Medicine, Bronx, NY
Albert Einstein College of Medicine (Bronx, New York, USA) ↗ ORCID0000-0002-7836-5072 ↗
Chaperone-mediated autophagy is the tidy form of self-digestion: a cytosolic chaperone carries one protein at a time to the lysosomal surface, where it unfolds and is threaded through a translocation complex. No vesicle is built. How it was regulated was largely unknown, which is a gap worth noticing given how much is known about the regulation of macroautophagy.
ARI2015 filled part of it and reversed two of the usual terms while doing so. The complex sitting on the lysosomal membrane here is mTORC2, not mTORC1, and it inhibits CMA through lysosomal Akt; the phosphatase PHLPP1 pushes the other way. What that kinase-phosphatase pair actually controls is the assembly and disassembly of the translocation complex — the gate, not the cargo.
Her own laboratory works on metabolic liver injury: fatty liver disease, hepatic tumorigenesis, and how failing autophagy contributes to age-related liver disease and to the progression from steatohepatitis to hepatocellular carcinoma.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2015 | M | Lysosomal mTORC2/PHLPP1/Akt regulate chaperone-mediated autophagy ARI2015 First author: a lysosomal mTORC2/PHLPP1/Akt axis controls chaperone-mediated autophagy by setting the assembly state of the translocation complex. |
Co-authors in the Atlas
People with a profile here who share at least one study with Esperanza Arias-Perez.
- Ana Maria Cuervo Worked out much of the machinery of chaperone-mediated autophagy, a pathway first described in Fred Dice's laboratory, and showed it declines with age