PMID- 38060380
OWN - NLM
STAT- MEDLINE
DCOM- 20240101
LR  - 20240210
IS  - 2211-1247 (Electronic)
VI  - 42
IP  - 12
DP  - 2023 Dec 26
TI  - Molecular determinants of the crosstalk between endosomal microautophagy and 
      chaperone-mediated autophagy.
PG  - 113529
LID - S2211-1247(23)01541-3 [pii]
LID - 10.1016/j.celrep.2023.113529 [doi]
AB  - Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are 
      pathways for selective degradation of cytosolic proteins in lysosomes and late 
      endosomes, respectively. These autophagic processes share as a first step the 
      recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 
      chaperone, raising the possibility of coordinated activity of both pathways. In 
      this work, we show the existence of a compensatory relationship between CMA and 
      eMI and identify a role for the chaperone protein Bag6 in triage and 
      internalization of eMI substrates into late endosomes. Association and dynamics 
      of Bag6 at the late endosome membrane change during starvation, a stressor that, 
      contrary to other autophagic pathways, causes a decline in eMI activity. 
      Collectively, these results show a coordinated function of eMI with CMA, identify 
      the interchangeable subproteome degraded by these pathways, and start to 
      elucidate the molecular mechanisms that facilitate the switch between them.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Krause, Gregory J
AU  - Krause GJ
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA.
FAU - Kirchner, Philipp
AU  - Kirchner P
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA.
FAU - Stiller, Barbara
AU  - Stiller B
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA.
FAU - Morozova, Kateryna
AU  - Morozova K
AD  - Department of Radiation Oncology, Weill Cornell School of Medicine, New York, NY 
      10021, USA.
FAU - Diaz, Antonio
AU  - Diaz A
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA.
FAU - Chen, Kuei-Ho
AU  - Chen KH
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, San Francisco, CA 94158, USA; The J. David Gladstone Institutes, San 
      Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of 
      California, San Francisco, San Francisco, CA 94158, USA.
FAU - Krogan, Nevan J
AU  - Krogan NJ
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, San Francisco, CA 94158, USA; The J. David Gladstone Institutes, San 
      Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of 
      California, San Francisco, San Francisco, CA 94158, USA.
FAU - Agullo-Pascual, Esperanza
AU  - Agullo-Pascual E
AD  - Microscopy CoRE, Dean's CoREs, Icahn School of Medicine at Mount Sinai, New York, 
      NY 10029, USA.
FAU - Clement, Cristina C
AU  - Clement CC
AD  - Department of Radiation Oncology, Weill Cornell School of Medicine, New York, NY 
      10021, USA.
FAU - Lindenau, Kristen
AU  - Lindenau K
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA.
FAU - Swaney, Danielle L
AU  - Swaney DL
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, San Francisco, CA 94158, USA; The J. David Gladstone Institutes, San 
      Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of 
      California, San Francisco, San Francisco, CA 94158, USA.
FAU - Dilipkumar, Shilpa
AU  - Dilipkumar S
AD  - Microscopy CoRE, Dean's CoREs, Icahn School of Medicine at Mount Sinai, New York, 
      NY 10029, USA.
FAU - Bravo-Cordero, Jose Javier
AU  - Bravo-Cordero JJ
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029, USA; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 
      New York, NY 10029, USA.
FAU - Santambrogio, Laura
AU  - Santambrogio L
AD  - Department of Radiation Oncology, Weill Cornell School of Medicine, New York, NY 
      10021, USA. Electronic address: las4011@med.cornell.edu.
FAU - Cuervo, Ana Maria
AU  - Cuervo AM
AD  - Department of Developmental and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY 10461, USA; Institute for Aging Studies, Albert Einstein 
      College of Medicine, Bronx, NY 10461, USA. Electronic address: 
      ana-maria.cuervo@einsteinmed.edu.
LA  - eng
GR  - R01 CA244780/CA/NCI NIH HHS/United States
GR  - U54 NS100717/NS/NINDS NIH HHS/United States
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - S10 OD021838/OD/NIH HHS/United States
GR  - T32 GM007491/GM/NIGMS NIH HHS/United States
GR  - RF1 AG054108/AG/NIA NIH HHS/United States
GR  - P30 AG038072/AG/NIA NIH HHS/United States
GR  - P30 CA196521/CA/NCI NIH HHS/United States
GR  - P01 AG031782/AG/NIA NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - R01 NS095435/NS/NINDS NIH HHS/United States
GR  - R01 DK098408/DK/NIDDK NIH HHS/United States
GR  - T32 GM007288/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20231206
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - *Chaperone-Mediated Autophagy
MH  - Microautophagy
MH  - Autophagy
MH  - Endosomes/metabolism
MH  - Lysosomes/metabolism
MH  - Molecular Chaperones/metabolism
PMC - PMC10807933
MID - NIHMS1954791
OTO - NOTNLM
OT  - Bag6
OT  - CP: Molecular biology
OT  - autophagy
OT  - chaperone
OT  - late endosome
OT  - lysosome
OT  - microautophagy
OT  - protein degradation
OT  - protein targeting
OT  - proteostasis
OT  - starvation
COIS- Declaration of interests A.M.C. is a co-founder and advisor to Selphagy (a Life 
      Biosciences program) and consults for Generian Pharmaceuticals and Cognition 
      Therapeuticals. The lab of N.J.K. has received support from Vir Biotechnology and 
      F. Hoffmann-La Roche. N.J.K. consults for Mount Sinai, Maze Therapeutics, and 
      Interline Therapeutics; is a shareholder in Tenaya Therapeutics; and has received 
      stocks from Maze Therapeutics and Interline Therapeutics.
EDAT- 2023/12/07 18:42
MHDA- 2024/01/02 11:42
PMCR- 2024/01/24
CRDT- 2023/12/07 12:36
PHST- 2022/01/11 00:00 [received]
PHST- 2023/09/12 00:00 [revised]
PHST- 2023/11/17 00:00 [accepted]
PHST- 2024/01/02 11:42 [medline]
PHST- 2023/12/07 18:42 [pubmed]
PHST- 2023/12/07 12:36 [entrez]
PHST- 2024/01/24 00:00 [pmc-release]
AID - S2211-1247(23)01541-3 [pii]
AID - 10.1016/j.celrep.2023.113529 [doi]
PST - ppublish
SO  - Cell Rep. 2023 Dec 26;42(12):113529. doi: 10.1016/j.celrep.2023.113529. Epub 2023 
      Dec 6.