PMID- 37798944
OWN - NLM
STAT- MEDLINE
DCOM- 20240429
LR  - 20240503
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 20
IP  - 4
DP  - 2024 Apr
TI  - Chaperone-mediated autophagy protects against hyperglycemic stress.
PG  - 752-768
LID - 10.1080/15548627.2023.2267415 [doi]
AB  - Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis 
      critical for cellular homeostasis and metabolism, and whose defects have been 
      associated with several human pathologies. While CMA has been well described in 
      mammals, functional evidence has only recently been documented in fish, opening 
      up new perspectives to tackle this function under a novel angle. Now we propose 
      to explore CMA functions in the rainbow trout (RT, Oncorhynchus mykiss), a fish 
      species recognized as a model organism of glucose intolerance and characterized 
      by the presence of two paralogs of the CMA-limiting factor Lamp2A (lysosomal 
      associated membrane protein 2A). To this end, we validated a fluorescent reporter 
      (KFERQ-PA-mCherry1) previously used to track functional CMA in mammalian cells, 
      in an RT hepatoma-derived cell line (RTH-149). We found that incubation of cells 
      with high-glucose levels (HG, 25 mM) induced translocation of the CMA reporter to 
      lysosomes and/or late endosomes in a KFERQ- and Lamp2A-dependent manner, as well 
      as reduced its half-life compared to the control (5 mM), thus demonstrating 
      increased CMA flux. Furthermore, we observed that activation of CMA upon HG 
      exposure was mediated by generation of mitochondrial reactive oxygen species, and 
      involving the antioxidant transcription factor Nfe2l2/Nrf2 (nfe2 like bZIP 
      transcription factor 2). Finally, we demonstrated that CMA plays an important 
      protective role against HG-induced stress, primarily mediated by one of the two 
      RT Lamp2As. Together, our results provide unequivocal evidence for CMA activity 
      existence in RT and highlight both the role and regulation of CMA during 
      glucose-related metabolic disorders.Abbreviations: AREs: antioxidant response 
      elements; CHC: alpha-cyano -4-hydroxycinnamic acid; Chr: chromosome; CMA: 
      chaperone-mediated autophagy; CT: control; DMF: dimethyl fumarate; Emi: endosomal 
      microautophagy; HG: high-glucose; HMOX1: heme oxygenase 1; H(2)O(2): hydrogen 
      peroxide; KFERQ: lysine-phenylalanine-glutamate-arginine-glutamine; LAMP1: 
      lysosomal associated membrane protein 1; LAMP2A: lysosomal associated membrane 
      protein 2A; MCC: Manders' correlation coefficient; Manders' correlation 
      coefficient Mo: morpholino oligonucleotide; NAC: N-acetyl cysteine; NFE2L2/NRF2: 
      NFE2 like bZIP transcription factor 2; PA-mCherry: photoactivable mCherry; PCC: 
      Pearson's correlation coefficient; ROS: reactive oxygen species; RT: rainbow 
      trout; siRNAs: small interfering RNAs; SOD: superoxide dismutase; Tsg101: tumor 
      susceptibility 101; TTFA: 2-thenoyltrifluoroacetone; WGD: whole-genome 
      duplication.
FAU - Velez, Emilio J
AU  - Velez EJ
AUID- ORCID: 0000-0002-6363-0697
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Schnebert, Simon
AU  - Schnebert S
AUID- ORCID: 0000-0003-0500-0002
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Goguet, Maxime
AU  - Goguet M
AUID- ORCID: 0009-0006-0615-0175
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Balbuena-Pecino, Sara
AU  - Balbuena-Pecino S
AUID- ORCID: 0000-0001-5101-4814
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Dias, Karine
AU  - Dias K
AUID- ORCID: 0009-0006-0931-0074
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Beauclair, Linda
AU  - Beauclair L
AUID- ORCID: 0000-0002-0124-2664
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Fontagne-Dicharry, Stephanie
AU  - Fontagne-Dicharry S
AUID- ORCID: 0000-0002-4366-4590
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Veron, Vincent
AU  - Veron V
AUID- ORCID: 0000-0003-1469-6443
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Depince, Alexandra
AU  - Depince A
AUID- ORCID: 0000-0001-7915-3410
AD  - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, 
      Rennes, France.
FAU - Beaumatin, Florian
AU  - Beaumatin F
AUID- ORCID: 0000-0001-6017-7172
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
FAU - Herpin, Amaury
AU  - Herpin A
AUID- ORCID: 0000-0002-0630-4027
AD  - INRAE, UR1037 Laboratory of Fish Physiology and Genomics, Campus de Beaulieu, 
      Rennes, France.
FAU - Seiliez, Iban
AU  - Seiliez I
AUID- ORCID: 0000-0002-2202-1756
AD  - Universite de Pau et des Pays de l'Adour, E2S UPPA, INRAE, UMR1419 Nutrition 
      Metabolisme et Aquaculture, Saint-Pee-sur-Nivelle, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231012
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Lysosomal-Associated Membrane Protein 2)
RN  - 0 (Molecular Chaperones)
SB  - IM
MH  - Animals
MH  - *Chaperone-Mediated Autophagy/drug effects/physiology/genetics
MH  - *Lysosomes/metabolism/drug effects
MH  - *Oncorhynchus mykiss/metabolism
MH  - *Glucose/metabolism
MH  - Hyperglycemia/metabolism/pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Lysosomal-Associated Membrane Protein 2/metabolism/genetics
MH  - Autophagy/physiology/genetics/drug effects
MH  - Molecular Chaperones/metabolism
MH  - Humans
PMC - PMC11062381
OTO - NOTNLM
OT  - CMA
OT  - Lamp2A
OT  - NFE2L2/NRF2
OT  - fish
OT  - glucose intolerance
OT  - metabolism
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2023/10/06 06:43
MHDA- 2024/04/30 04:21
PMCR- 2024/10/05
CRDT- 2023/10/06 02:13
PHST- 2024/10/05 00:00 [pmc-release]
PHST- 2024/04/30 04:21 [medline]
PHST- 2023/10/06 06:43 [pubmed]
PHST- 2023/10/06 02:13 [entrez]
AID - 2267415 [pii]
AID - 10.1080/15548627.2023.2267415 [doi]
PST - ppublish
SO  - Autophagy. 2024 Apr;20(4):752-768. doi: 10.1080/15548627.2023.2267415. Epub 2023 
      Oct 12.