PMID- 32613295
OWN - NLM
STAT- MEDLINE
DCOM- 20210226
LR  - 20210226
IS  - 1432-0983 (Electronic)
IS  - 0172-8083 (Linking)
VI  - 66
IP  - 5
DP  - 2020 Oct
TI  - Loss of ERAD bridging factor UBX2 modulates lipid metabolism and leads to ER 
      stress-associated apoptosis during cadmium toxicity in Saccharomyces cerevisiae.
PG  - 1003-1017
LID - 10.1007/s00294-020-01090-y [doi]
AB  - The endoplasmic reticulum (ER) stress potentially activates the unfolded protein 
      response (UPR) and ER-associated protein degradation (ERAD) as quality-control 
      mechanisms. During ERAD process, the ERAD adaptor protein Ubx2 serves as a 
      bridging factor and transports the misfolded proteins from the ER to the cytosol 
      for subsequent ubiquitylation and proteasomal degradation. Cadmium (Cd) is a 
      toxic metal that initiates ER stress and has an impact on lipid homeostasis and 
      this study focuses on the synergistic impact of Cd exposure and ERAD (using ubx2∆ 
      strain). With Cd exposure in ubx2∆ strain, we observed stunted growth and 
      induction of ER stress. The ER stress was confirmed by measuring the expression 
      of UPR marker (Kar2p), and mRNA expression of ER stress-responsive genes (HAC1, 
      IRE1, ERO1, and PDI1), heat shock responsive genes (HSP104 and HSP60), ERAD 
      pathway genes (DOA10, CDC48, HRD1, and YOS9), and proteasome regulators (UBI14, 
      and RPN4). We also observed aberrant membrane morphology with DiOC6 staining, and 
      interrupted mitochondria with mitotracker dye using microscopic analysis. The 
      cell's inability to relieve stress through adaptive response results in apoptosis 
      and was assessed using acridine orange (AO)-ethidium bromide (EtBr) staining. In 
      ubx2∆ strain, there was reduction in triacylglycerol (TAG) and lipid droplets 
      (LDs), and increase in the phospholipids. The mRNA expression of lipid metabolic 
      genes (LRO1, DGA1, ARE1, ARE2, and OLE1) supported the lipid pattern observed. 
      Collectively, our data suggest that in Saccharomyces cerevisiae, the Cd exposure 
      on ubx2∆ strain induced cellular stress and has an impact on ERAD, UPR, and LD 
      homeostasis.
FAU - Rajakumar, Selvaraj
AU  - Rajakumar S
AD  - Biomembrane Lab, Department of Biochemistry, School of Life Science, 
      Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India.
AD  - Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj 
      University, Madurai, Tamil Nadu, 625021, India.
FAU - Vijayakumar, Rajendran
AU  - Vijayakumar R
AD  - Biomembrane Lab, Department of Biochemistry, School of Life Science, 
      Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India.
FAU - Abhishek, Albert
AU  - Abhishek A
AD  - Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj 
      University, Madurai, Tamil Nadu, 625021, India.
FAU - Selvam, Govindan Sadasivam
AU  - Selvam GS
AD  - Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj 
      University, Madurai, Tamil Nadu, 625021, India.
FAU - Nachiappan, Vasanthi
AU  - Nachiappan V
AUID- ORCID: 0000-0001-9891-3657
AD  - Biomembrane Lab, Department of Biochemistry, School of Life Science, 
      Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India. 
      vasanthibch@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200701
PL  - United States
TA  - Curr Genet
JT  - Current genetics
JID - 8004904
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Lipids)
RN  - 0 (Phospholipids)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Triglycerides)
RN  - 0 (UBX2 protein, S cerevisiae)
RN  - 00BH33GNGH (Cadmium)
SB  - IM
MH  - *Apoptosis
MH  - Cadmium/*toxicity
MH  - Carrier Proteins/genetics/*metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - *Endoplasmic Reticulum Stress
MH  - *Endoplasmic Reticulum-Associated Degradation
MH  - Gene Expression Regulation, Fungal
MH  - Genes, Fungal
MH  - Lipid Droplets/metabolism
MH  - *Lipid Metabolism
MH  - Membrane Lipids/metabolism
MH  - Mitochondria/drug effects/ultrastructure
MH  - Phospholipids/metabolism
MH  - Saccharomyces cerevisiae/*drug effects/genetics/growth & development/physiology
MH  - Saccharomyces cerevisiae Proteins/genetics/*metabolism
MH  - Triglycerides/metabolism
MH  - Unfolded Protein Response
OTO - NOTNLM
OT  - ERAD
OT  - Lipid droplet and yeast
OT  - UPR
EDAT- 2020/07/03 06:00
MHDA- 2021/02/27 06:00
CRDT- 2020/07/03 06:00
PHST- 2020/03/04 00:00 [received]
PHST- 2020/06/22 00:00 [accepted]
PHST- 2020/06/08 00:00 [revised]
PHST- 2020/07/03 06:00 [pubmed]
PHST- 2021/02/27 06:00 [medline]
PHST- 2020/07/03 06:00 [entrez]
AID - 10.1007/s00294-020-01090-y [pii]
AID - 10.1007/s00294-020-01090-y [doi]
PST - ppublish
SO  - Curr Genet. 2020 Oct;66(5):1003-1017. doi: 10.1007/s00294-020-01090-y. Epub 2020 
      Jul 1.