PMID- 32005807
OWN - NLM
STAT- MEDLINE
DCOM- 20200511
LR  - 20240423
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 31
TI  - Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo.
PG  - 645
LID - 10.1038/s41467-019-14164-4 [doi]
LID - 645
AB  - Autophagy malfunctioning occurs in multiple human disorders, making attractive 
      the idea of chemically modulating it with therapeutic purposes. However, for many 
      types of autophagy, a clear understanding of tissue-specific differences in their 
      activity and regulation is missing because of lack of methods to monitor these 
      processes in vivo. Chaperone-mediated autophagy (CMA) is a selective type of 
      autophagy that until now has only been studied in vitro and not in the tissue 
      context at single cell resolution. Here, we develop a transgenic reporter mouse 
      that allows dynamic measurement of CMA activity in vivo using image-based 
      procedures. We identify previously unknown spatial and temporal differences in 
      CMA activity in multiple organs and in response to stress. We illustrate the 
      versatility of this model for monitoring CMA in live animals, organotypic 
      cultures and cell cultures from these mice, and provide practical examples of 
      multiorgan response to drugs that modulate CMA.
FAU - Dong, S
AU  - Dong S
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY, 10461, USA.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, 
      10461, USA.
FAU - Aguirre-Hernandez, C
AU  - Aguirre-Hernandez C
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY, 10461, USA.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, 
      10461, USA.
AD  - Department of Medicine, Division of Hematology and Medical Oncology, Icahn School 
      of Medicine at Mount Sinai, New York, 10029, NY, USA.
AD  - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 
      10029, NY, USA.
FAU - Scrivo, A
AU  - Scrivo A
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY, 10461, USA.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, 
      10461, USA.
FAU - Eliscovich, C
AU  - Eliscovich C
AUID- ORCID: 0000-0001-7653-5536
AD  - Department of Medicine Marion Liver Research Center, Albert Einstein College of 
      Medicine, Bronx, 10461, NY, USA.
FAU - Arias, E
AU  - Arias E
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, 
      10461, USA. esperanza.arias-perez@einsteinmed.org.
AD  - Department of Medicine Marion Liver Research Center, Albert Einstein College of 
      Medicine, Bronx, 10461, NY, USA. esperanza.arias-perez@einsteinmed.org.
FAU - Bravo-Cordero, J J
AU  - Bravo-Cordero JJ
AD  - Department of Medicine, Division of Hematology and Medical Oncology, Icahn School 
      of Medicine at Mount Sinai, New York, 10029, NY, USA. 
      josejavier.bravo-cordero@mssm.edu.
AD  - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, 
      10029, NY, USA. josejavier.bravo-cordero@mssm.edu.
FAU - Cuervo, A M
AU  - Cuervo AM
AUID- ORCID: 0000-0002-0771-700X
AD  - Department of Development and Molecular Biology, Albert Einstein College of 
      Medicine, Bronx, NY, 10461, USA. ana-maria.cuervo@einsteinmed.org.
AD  - Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, NY, 
      10461, USA. ana-maria.cuervo@einsteinmed.org.
AD  - Department of Medicine, Division of Hematology and Medical Oncology, Icahn School 
      of Medicine at Mount Sinai, New York, 10029, NY, USA. 
      ana-maria.cuervo@einsteinmed.org.
LA  - eng
GR  - U54 NS100717/NS/NINDS NIH HHS/United States
GR  - R01 AG021904/AG/NIA NIH HHS/United States
GR  - P30 DK041296/DK/NIDDK NIH HHS/United States
GR  - R01 DK124308/DK/NIDDK NIH HHS/United States
GR  - R37 AG021904/AG/NIA NIH HHS/United States
GR  - K22 CA196750/CA/NCI NIH HHS/United States
GR  - RF1 AG054108/AG/NIA NIH HHS/United States
GR  - P30 AG038072/AG/NIA NIH HHS/United States
GR  - R01 DK098408/DK/NIDDK NIH HHS/United States
GR  - P30 CA196521/CA/NCI NIH HHS/United States
GR  - P01 AG031782/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200131
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Molecular Chaperones)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - *Chaperone-Mediated Autophagy
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Liver/metabolism
MH  - Lysosomal-Associated Membrane Protein 2/genetics/metabolism
MH  - Lysosomes/genetics/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Chaperones/genetics/metabolism
PMC - PMC6994528
COIS- A.M.C. consults for Neuropore (La Jolla, CA, USA) and is cofounder of Selphagy 
      Therapeutics (Boston, MA, USA). The rest of authors declare no competing 
      interest.
EDAT- 2020/02/02 06:00
MHDA- 2020/05/12 06:00
PMCR- 2020/01/31
CRDT- 2020/02/02 06:00
PHST- 2018/10/16 00:00 [received]
PHST- 2019/12/06 00:00 [accepted]
PHST- 2020/02/02 06:00 [entrez]
PHST- 2020/02/02 06:00 [pubmed]
PHST- 2020/05/12 06:00 [medline]
PHST- 2020/01/31 00:00 [pmc-release]
AID - 10.1038/s41467-019-14164-4 [pii]
AID - 14164 [pii]
AID - 10.1038/s41467-019-14164-4 [doi]
PST - epublish
SO  - Nat Commun. 2020 Jan 31;11(1):645. doi: 10.1038/s41467-019-14164-4.