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primary topic: Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast

Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast
type: AcademicArticle
type: Article
abstract: Under prolonged starvation, mammalian cells activate chaperone-mediated autophagy (CMA) that degrades cellular proteins containing KFERQ-like motifs via lysosomes. During CMA, the lysosomal membrane protein LAMP2A acts as an essential receptor for the HSPA8/HSC70-CMA substrate complex. Thus, the evidence of CMA in organisms lacking LAMP2A on lysosomes/vacuoles is still lacking. Here, we examined the fate of proteins containing such motifs in S. cerevisiae that lack the CMA receptor on vacuoles. Intriguingly, we found that even in the absence of LAMP2A, proteins containing such motifs translocate into vacuoles upon prolonged starvation. We report for the first time that phosphatidylserine acts as an Hsp70-family protein-substrate receptor on the vacuolar membrane to facilitate the substrate translocation into vacuoles. As the newly discovered degradation pathway is dependent upon cytosolic Hsp70 (as in CMA) as well as the ESCRT complex, and involves invagination of the vacuolar membrane, we refer to it as chaperone-mediated microautophagy. Taken together, this study has led to the identification of a novel cellular pathway in S. cerevisiae that facilitates the clearance of cellular proteins under chronic stress.Abbreviations: CMA: chaperone-mediated autophagy; CMA-tag: KFERQ motif; ESCRT: endosomal sorting complexes required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HSPA8: heat shock protein 8; LAMP2A: lysosomal-associated membrane protein type 2A; Lact-C2: lactadherin C2 domain; PAmCherry: photoactivatable mCherry; PBS: phosphate-buffered saline; PS: phosphatidylserine; PtdIns4P: phosphatidylinositol-4-phosphate; RFP: red fluorescent protein; TBST: Tris-buffered saline with Tween 20.
date: 2026-07-22
volume: 22
issue: 7
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
has document: Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast (HTML)
subject: QR Microbiology

Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast (HTML)
type: Document
has file: references (1).bib
has part: references (1).bib

Informa UK Limited
type: Organization

Autophagy
type: Collection

Namra Farooqi
type: Person
given name: Namra
family name: Farooqi

Krishna Upadhayay
type: Person
given name: Krishna
family name: Upadhayay

Bhagyashree Rabha
type: Person
given name: Bhagyashree
family name: Rabha

Kamalesh Verma
type: Person
given name: Kamalesh
family name: Verma

Adarsh Mishra
type: Person
given name: Adarsh
family name: Mishra

Pushpender Bhardwaj
type: Person
given name: Pushpender
family name: Bhardwaj

Ramandeep Singh
type: Person
given name: Ramandeep
family name: Singh

Deepak Sharma
type: Person
given name: Deepak
family name: Sharma

HTML Summary of #3488 Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast
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primary topic: Unravelling chaperone-mediated microautophagy targeting KFERQ-like motif containing proteins in yeast

QR Microbiology
type: Concept