Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway

Pedro Barreto; Charlene Dambire; Gunjan Sharma; Jorge Vicente; Rory Osborne; Juliana Yassitepe; Daniel J. Gibbs; Ivan G. Maia; Michael J. Holdsworth; Paulo Arruda

doi:10.1016/j.cub.2022.01.037

Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway

Pedro Barreto, Charlene Dambire, Gunjan Sharma, Jorge Vicente, Rory Osborne, Juliana Yassitepe, Daniel J. Gibbs, Ivan G. Maia, Michael J. Holdsworth, Paulo Arruda

Biosciences

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Abstract

Mitochondrial retrograde signaling is an important component of intracellular stress signaling in eukaryotes. UNCOUPLING PROTEIN (UCP)1 is an abundant plant inner-mitochondrial membrane protein with multiple functions including uncoupled respiration and amino-acid transport¹^,² that influences broad abiotic stress responses. Although the mechanism(s) through which this retrograde function acts is unknown, overexpression of UCP1 activates expression of hypoxia (low oxygen)-associated nuclear genes.³^,⁴ Here we show in Arabidopsis thaliana that UCP1 influences nuclear gene expression and physiological response by inhibiting the cytoplasmic PLANT CYSTEINE OXIDASE (PCO) branch of the PROTEOLYSIS (PRT)6 N-degron pathway, a major mechanism of oxygen and nitric oxide (NO) sensing.⁵ Overexpression of UCP1 (UCP1ox) resulted in the stabilization of an artificial PCO N-degron pathway substrate, and stability of this reporter protein was influenced by pharmacological interventions that control UCP1 activity. Hypoxia and salt-tolerant phenotypes observed in UCP1ox lines resembled those observed for the PRT6 N-recognin E3 ligase mutant prt6-1. Genetic analysis showed that UCP1 regulation of hypoxia responses required the activity of PCO N-degron pathway ETHYLENE RESPONSE FACTOR (ERF)VII substrates. Transcript expression analysis indicated that UCP1 regulation of hypoxia-related gene expression is a normal component of seedling development. Our results show that mitochondrial retrograde signaling represses the PCO N-degron pathway, enhancing substrate function, thus facilitating downstream stress responses. This work reveals a novel mechanism through which mitochondrial retrograde signaling influences nuclear response to hypoxia by inhibition of an ancient cytoplasmic pathway of eukaryotic oxygen sensing.

Original language	English
Pages (from-to)	1403-1411.e4
Journal	Current Biology
Volume	32
Issue number	6
Early online date	2 Feb 2022
DOIs	https://doi.org/10.1016/j.cub.2022.01.037
Publication status	Published - 28 Mar 2022

Bibliographical note

Acknowledgments
P.B. was a FAPESP (2014/17634-5, 2015/24881-1, and 2017/22745-9) and CAPES (88887.572598/2020-00) postdoc research fellow. This work was supported by the Biotechnology and Biological Sciences Research Council (grant nos. BB/R002428/1 and BB/S005293/1) to M.J.H. P.A. was supported by the FAPESP grant 2016/23218-0 through the Genomics for Climate Change Research Center (GCCRC). I.G.M. is a CNPq productivity research fellow. D.J.G. and R.O. were supported by the European Research Council (ERC Starting Grant 715441-GasPlaNt).

Keywords

ERFVII
N-degron pathway
UCP1
abiotic stress
mitochondria
oxygen sensing
retrograde signaling

ASJC Scopus subject areas

Neuroscience(all)
Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)

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@article{2f7581cd8568400687edd6dbe24ba983,

title = "Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway",

abstract = "Mitochondrial retrograde signaling is an important component of intracellular stress signaling in eukaryotes. UNCOUPLING PROTEIN (UCP)1 is an abundant plant inner-mitochondrial membrane protein with multiple functions including uncoupled respiration and amino-acid transport1,2 that influences broad abiotic stress responses. Although the mechanism(s) through which this retrograde function acts is unknown, overexpression of UCP1 activates expression of hypoxia (low oxygen)-associated nuclear genes.3,4 Here we show in Arabidopsis thaliana that UCP1 influences nuclear gene expression and physiological response by inhibiting the cytoplasmic PLANT CYSTEINE OXIDASE (PCO) branch of the PROTEOLYSIS (PRT)6 N-degron pathway, a major mechanism of oxygen and nitric oxide (NO) sensing.5 Overexpression of UCP1 (UCP1ox) resulted in the stabilization of an artificial PCO N-degron pathway substrate, and stability of this reporter protein was influenced by pharmacological interventions that control UCP1 activity. Hypoxia and salt-tolerant phenotypes observed in UCP1ox lines resembled those observed for the PRT6 N-recognin E3 ligase mutant prt6-1. Genetic analysis showed that UCP1 regulation of hypoxia responses required the activity of PCO N-degron pathway ETHYLENE RESPONSE FACTOR (ERF)VII substrates. Transcript expression analysis indicated that UCP1 regulation of hypoxia-related gene expression is a normal component of seedling development. Our results show that mitochondrial retrograde signaling represses the PCO N-degron pathway, enhancing substrate function, thus facilitating downstream stress responses. This work reveals a novel mechanism through which mitochondrial retrograde signaling influences nuclear response to hypoxia by inhibition of an ancient cytoplasmic pathway of eukaryotic oxygen sensing.",

keywords = "ERFVII, N-degron pathway, UCP1, abiotic stress, mitochondria, oxygen sensing, retrograde signaling",

author = "Pedro Barreto and Charlene Dambire and Gunjan Sharma and Jorge Vicente and Rory Osborne and Juliana Yassitepe and Gibbs, {Daniel J.} and Maia, {Ivan G.} and Holdsworth, {Michael J.} and Paulo Arruda",

note = "Acknowledgments P.B. was a FAPESP (2014/17634-5, 2015/24881-1, and 2017/22745-9) and CAPES (88887.572598/2020-00) postdoc research fellow. This work was supported by the Biotechnology and Biological Sciences Research Council (grant nos. BB/R002428/1 and BB/S005293/1) to M.J.H. P.A. was supported by the FAPESP grant 2016/23218-0 through the Genomics for Climate Change Research Center (GCCRC). I.G.M. is a CNPq productivity research fellow. D.J.G. and R.O. were supported by the European Research Council (ERC Starting Grant 715441-GasPlaNt).",

year = "2022",

month = mar,

day = "28",

doi = "10.1016/j.cub.2022.01.037",

language = "English",

volume = "32",

pages = "1403--1411.e4",

journal = "Current Biology",

issn = "0960-9822",

publisher = "Elsevier",

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T1 - Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway

AU - Barreto, Pedro

AU - Dambire, Charlene

AU - Sharma, Gunjan

AU - Vicente, Jorge

AU - Osborne, Rory

AU - Yassitepe, Juliana

AU - Gibbs, Daniel J.

AU - Maia, Ivan G.

AU - Holdsworth, Michael J.

AU - Arruda, Paulo

N1 - Acknowledgments P.B. was a FAPESP (2014/17634-5, 2015/24881-1, and 2017/22745-9) and CAPES (88887.572598/2020-00) postdoc research fellow. This work was supported by the Biotechnology and Biological Sciences Research Council (grant nos. BB/R002428/1 and BB/S005293/1) to M.J.H. P.A. was supported by the FAPESP grant 2016/23218-0 through the Genomics for Climate Change Research Center (GCCRC). I.G.M. is a CNPq productivity research fellow. D.J.G. and R.O. were supported by the European Research Council (ERC Starting Grant 715441-GasPlaNt).

PY - 2022/3/28

Y1 - 2022/3/28

N2 - Mitochondrial retrograde signaling is an important component of intracellular stress signaling in eukaryotes. UNCOUPLING PROTEIN (UCP)1 is an abundant plant inner-mitochondrial membrane protein with multiple functions including uncoupled respiration and amino-acid transport1,2 that influences broad abiotic stress responses. Although the mechanism(s) through which this retrograde function acts is unknown, overexpression of UCP1 activates expression of hypoxia (low oxygen)-associated nuclear genes.3,4 Here we show in Arabidopsis thaliana that UCP1 influences nuclear gene expression and physiological response by inhibiting the cytoplasmic PLANT CYSTEINE OXIDASE (PCO) branch of the PROTEOLYSIS (PRT)6 N-degron pathway, a major mechanism of oxygen and nitric oxide (NO) sensing.5 Overexpression of UCP1 (UCP1ox) resulted in the stabilization of an artificial PCO N-degron pathway substrate, and stability of this reporter protein was influenced by pharmacological interventions that control UCP1 activity. Hypoxia and salt-tolerant phenotypes observed in UCP1ox lines resembled those observed for the PRT6 N-recognin E3 ligase mutant prt6-1. Genetic analysis showed that UCP1 regulation of hypoxia responses required the activity of PCO N-degron pathway ETHYLENE RESPONSE FACTOR (ERF)VII substrates. Transcript expression analysis indicated that UCP1 regulation of hypoxia-related gene expression is a normal component of seedling development. Our results show that mitochondrial retrograde signaling represses the PCO N-degron pathway, enhancing substrate function, thus facilitating downstream stress responses. This work reveals a novel mechanism through which mitochondrial retrograde signaling influences nuclear response to hypoxia by inhibition of an ancient cytoplasmic pathway of eukaryotic oxygen sensing.

AB - Mitochondrial retrograde signaling is an important component of intracellular stress signaling in eukaryotes. UNCOUPLING PROTEIN (UCP)1 is an abundant plant inner-mitochondrial membrane protein with multiple functions including uncoupled respiration and amino-acid transport1,2 that influences broad abiotic stress responses. Although the mechanism(s) through which this retrograde function acts is unknown, overexpression of UCP1 activates expression of hypoxia (low oxygen)-associated nuclear genes.3,4 Here we show in Arabidopsis thaliana that UCP1 influences nuclear gene expression and physiological response by inhibiting the cytoplasmic PLANT CYSTEINE OXIDASE (PCO) branch of the PROTEOLYSIS (PRT)6 N-degron pathway, a major mechanism of oxygen and nitric oxide (NO) sensing.5 Overexpression of UCP1 (UCP1ox) resulted in the stabilization of an artificial PCO N-degron pathway substrate, and stability of this reporter protein was influenced by pharmacological interventions that control UCP1 activity. Hypoxia and salt-tolerant phenotypes observed in UCP1ox lines resembled those observed for the PRT6 N-recognin E3 ligase mutant prt6-1. Genetic analysis showed that UCP1 regulation of hypoxia responses required the activity of PCO N-degron pathway ETHYLENE RESPONSE FACTOR (ERF)VII substrates. Transcript expression analysis indicated that UCP1 regulation of hypoxia-related gene expression is a normal component of seedling development. Our results show that mitochondrial retrograde signaling represses the PCO N-degron pathway, enhancing substrate function, thus facilitating downstream stress responses. This work reveals a novel mechanism through which mitochondrial retrograde signaling influences nuclear response to hypoxia by inhibition of an ancient cytoplasmic pathway of eukaryotic oxygen sensing.

KW - ERFVII

KW - N-degron pathway

KW - UCP1

KW - abiotic stress

KW - mitochondria

KW - oxygen sensing

KW - retrograde signaling

U2 - 10.1016/j.cub.2022.01.037

DO - 10.1016/j.cub.2022.01.037

M3 - Article

C2 - 35114096

SN - 0960-9822

VL - 32

SP - 1403-1411.e4

JO - Current Biology

JF - Current Biology

IS - 6

ER -

Mitochondrial retrograde signaling through UCP1-mediated inhibition of the plant oxygen-sensing pathway

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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