NQO1 Binds and Supports SIRT1 Function
Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+ for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-06-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.671929/full |
id |
doaj-0de2676c8aa2428da43ad35b8ace3cdd |
---|---|
record_format |
Article |
spelling |
doaj-0de2676c8aa2428da43ad35b8ace3cdd2021-06-21T04:45:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-06-011210.3389/fphar.2021.671929671929NQO1 Binds and Supports SIRT1 FunctionPeter Tsvetkov0Julia Adler1Romano Strobelt2Yaarit Adamovich3Gad Asher4Nina Reuven5Yosef Shaul6Broad Institute of Harvard and MIT, Cambridge, MA, United StatesDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelDepartment of Molecular Genetics Weizmann Institute of Science, Rehovot, IsraelSilent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+ for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD+ dependent deacetylase may act as a rheostat in sensing mitochondrial stress.https://www.frontiersin.org/articles/10.3389/fphar.2021.671929/fullquinone oxidoreductase 1NADH/NAD ratioSIRT1 activityPGC1 alphamitochondria stress |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peter Tsvetkov Julia Adler Romano Strobelt Yaarit Adamovich Gad Asher Nina Reuven Yosef Shaul |
spellingShingle |
Peter Tsvetkov Julia Adler Romano Strobelt Yaarit Adamovich Gad Asher Nina Reuven Yosef Shaul NQO1 Binds and Supports SIRT1 Function Frontiers in Pharmacology quinone oxidoreductase 1 NADH/NAD ratio SIRT1 activity PGC1 alpha mitochondria stress |
author_facet |
Peter Tsvetkov Julia Adler Romano Strobelt Yaarit Adamovich Gad Asher Nina Reuven Yosef Shaul |
author_sort |
Peter Tsvetkov |
title |
NQO1 Binds and Supports SIRT1 Function |
title_short |
NQO1 Binds and Supports SIRT1 Function |
title_full |
NQO1 Binds and Supports SIRT1 Function |
title_fullStr |
NQO1 Binds and Supports SIRT1 Function |
title_full_unstemmed |
NQO1 Binds and Supports SIRT1 Function |
title_sort |
nqo1 binds and supports sirt1 function |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2021-06-01 |
description |
Silent information regulator 2-related enzyme 1 (SIRT1) is an NAD+-dependent class III deacetylase and a key component of the cellular metabolic sensing pathway. The requirement of NAD+ for SIRT1 activity led us to assume that NQO1, an NADH oxidoreductase producing NAD+, regulates SIRT1 activity. We show here that SIRT1 is capable of increasing NQO1 (NAD(P)H Dehydrogenase Quinone 1) transcription and protein levels. NQO1 physically interacts with SIRT1 but not with an enzymatically dead SIRT1 H363Y mutant. The interaction of NQO1 with SIRT1 is markedly increased under mitochondrial inhibition. Interestingly, under this condition the nuclear pool of NQO1 is elevated. Depletion of NQO1 compromises the role of SIRT1 in inducing transcription of several target genes and eliminates the protective role of SIRT1 following mitochondrial inhibition. Our results suggest that SIRT1 and NQO1 form a regulatory loop where SIRT1 regulates NQO1 expression and NQO1 binds and mediates the protective role of SIRT1 during mitochondrial stress. The interplay between an NADH oxidoreductase enzyme and an NAD+ dependent deacetylase may act as a rheostat in sensing mitochondrial stress. |
topic |
quinone oxidoreductase 1 NADH/NAD ratio SIRT1 activity PGC1 alpha mitochondria stress |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2021.671929/full |
work_keys_str_mv |
AT petertsvetkov nqo1bindsandsupportssirt1function AT juliaadler nqo1bindsandsupportssirt1function AT romanostrobelt nqo1bindsandsupportssirt1function AT yaaritadamovich nqo1bindsandsupportssirt1function AT gadasher nqo1bindsandsupportssirt1function AT ninareuven nqo1bindsandsupportssirt1function AT yosefshaul nqo1bindsandsupportssirt1function |
_version_ |
1721368830142316544 |