Loss of USF2 promotes proliferation, migration and mitophagy in a redox-dependent manner.

Compromised mitochondria Migration Mitophagy Proliferation Upstream stimulatory factor 2 (USF2)

Journal

Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639

Informations de publication

Date de publication:
10 2020
Historique:
received: 28 08 2020
revised: 02 10 2020
accepted: 04 10 2020
pubmed: 16 10 2020
medline: 22 6 2021
entrez: 15 10 2020
Statut: ppublish

Résumé

The upstream stimulatory factor 2 (USF2) is a transcription factor implicated in several cellular processes and among them, tumor development seems to stand out. However, the data with respect to the role of USF2 in tumor development are conflicting suggesting that it acts either as tumor promoter or suppressor. Here we show that absence of USF2 promotes proliferation and migration. Thereby, we reveal a previously unknown function of USF2 in mitochondrial homeostasis. Mechanistically, we demonstrate that deficiency of USF2 promotes survival by inducing mitophagy in a ROS-sensitive manner by activating both ERK1/2 and AKT. Altogether, this study supports USF2's function as tumor suppressor and highlights its novel role for mitochondrial function and energy homeostasis thereby linking USF2 to conditions such as insulin resistance, type-2 diabetes mellitus, and the metabolic syndrome.

Identifiants

pubmed: 33059314
pii: S2213-2317(20)30955-1
doi: 10.1016/j.redox.2020.101750
pmc: PMC7566946
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101750

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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Auteurs

Tabughang Franklin Chi (TF)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.

Fawzi Khoder-Agha (F)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.

Daniela Mennerich (D)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.

Sakari Kellokumpu (S)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.

IIkka Miinalainen (I)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland.

Thomas Kietzmann (T)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address: Thomas.Kietzmann@oulu.fi.

Elitsa Y Dimova (EY)

Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland. Electronic address: Elitsa.Dimova@oulu.fi.

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Classifications MeSH