The Cellular Localization of the p42 and p46 Oligoadenylate Synthetase 1 Isoforms and Their Impact on Mitochondrial Respiration.
CaaX motif
ISG
OAS1
cellular localization
high resolution respirometry
mitochondrial transmembrane potential
oroboros
oxygen consumption rate
type 1 inteferon
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
04 12 2019
04 12 2019
Historique:
received:
15
10
2019
revised:
28
11
2019
accepted:
02
12
2019
entrez:
11
12
2019
pubmed:
11
12
2019
medline:
22
9
2020
Statut:
epublish
Résumé
The importance of the IFN-induced oligoadenylate synthetase (OAS) proteins and the OAS/RNase L pathway in the innate response against viral pathogens is well-established, however the observed differences in anti-viral activity between the human OAS1 p46 and p42 isoforms are not fully understood. The protein expression of these isoforms is determined by the SNP rs10774671, either being an A or a G allele resulting in expression of either the p42 or the p46 isoform. Using fluorescence microscopy and immunoblot analysis of fractionated cell samples, we show here that the CaaX motif is of key importance to the cellular localization. The OAS1 p42 isoform is mainly located in the cytosol, whereas the p46 isoform with a C-terminal CaaX motif is translocated to membranous organelles, like the mitochondria. We furthermore observed differences between p42 and p46 in their effect on mitochondrial physiology using high resolution respirometry and fluorometry. Overexpression of OAS1 p42 and IFN-β treatment of HeLa cells (AA genotype) resulted in significantly increased respiration, which was not seen with p46 overexpression. The difference in subcellular localization and mitochondrial effect of these two OAS1 isoforms might help to explain the anti-viral mechanisms that differentiate these proteins.
Identifiants
pubmed: 31817188
pii: v11121122
doi: 10.3390/v11121122
pmc: PMC6950736
pii:
doi:
Substances chimiques
Interferon-beta
77238-31-4
OAS1 protein, human
EC 2.7.7.-
2',5'-Oligoadenylate Synthetase
EC 2.7.7.84
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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