Mitochondrial dysfunction induces SESN2 gene expression through Activating Transcription Factor 4

Cell Cycle
A A GaraevaA G Evstafieva

Abstract

We found that inhibitors of mitochondrial respiratory chain complexes III (myxothiazol) and I (piericidin A) in some epithelial carcinoma cell lines induce transcription of the p53-responsive SESN2 gene that plays an important role in stress response and homeostatic regulation. However, the effect did not depend on p53 because i) there was no induction of p53 after the treatment with piericidin A; ii) after the treatment with myxothiazol the peak of SESN2 gene upregulation occurred as early as 5h, before the onset of p53 activation (13h); iii) a supplementation with uridine that abolishes the p53 activation in response to myxothiazol did not abrogate the induction of SESN2 transcripts; iv) in the p53 negative HCT116 p53 -/- cells SESN2 transcription could be also induced by myxothiazol. In response to the respiratory chain inhibitors we observed an induction of ATF4, the key transcription factor of the integrated stress response (ISR). We found that the induction of SESN2 transcripts could be prevented by the ISR inhibitory small molecule ISRIB. Also, by inhibiting or overexpressing ATF4 with specific shRNA or ATF4-expressing constructs, respectively, we have confirmed the role of ATF4 in the SESN2 gene upregulation induced by ...Continue Reading

References

Jan 6, 2004·Science·Lyubomir T VassilevEmily A Liu
Nov 16, 2005·Nature Medicine·Anna A SablinaPeter M Chumakov
Oct 17, 2008·Molekuliarnaia biologiia·N I ZakharovaA G Evstaf'eva
Dec 23, 2008·Seminars in Cancer Biology·Ivan A OlovnikovPeter M Chumakov
Apr 21, 2009·Cell Cycle·Maria Chiara MaiuriGuido Kroemer
Oct 6, 2009·Trends in Endocrinology and Metabolism : TEM·Michael S KilbergNan Su
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anastasia A KhutornenkoAlexandra G Evstafieva
Mar 23, 2011·Biochemistry. Biokhimii︠a︡·A O Zheltukhin, P M Chumakov
Sep 20, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nels OlsonAlbert van der Vliet
Oct 26, 2011·Molecular and Cellular Biology·Sebastian AlersBjörn Stork
Nov 22, 2011·Molecular Cell·Nirmalya SenSanjeev Das
Feb 22, 2012·Journal of Cell Science·Judith HagenbuchnerMichael J Ausserlechner
May 16, 2012·Advances in Nutrition·Thomas D Baird, Ronald C Wek
Jul 4, 2012·Free Radical Biology & Medicine·Bo Yeon ShinSung Hwan Ki
Sep 11, 2012·Cell Metabolism·Jun Hee LeeMichael Karin
May 24, 2013·American Journal of Physiology. Renal Physiology·Masayuki IshiharaYoshio Terada
Aug 7, 2013·Molecular Oncology·Ansgar BrüningKlaus Friese
Jun 21, 2014·Nature Communications·Hwan-Woo ParkJun Hee Lee
Nov 5, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alex MorrisonJi Li

❮ Previous
Next ❯

Citations

Mar 17, 2016·Radiation and Environmental Biophysics·Yue-Can ZengRong Wu
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Dibyendu K PandaAndrew C Karaplis
Apr 15, 2020·PloS One·Irina E KovalevaAndrei V Budanov
May 7, 2020·Experimental and Therapeutic Medicine·Seunghyeong LeeKeun-Gyu Park
May 15, 2019·Biology·Ian Weidling, Russell H Swerdlow
Feb 2, 2019·Journal of Clinical Biochemistry and Nutrition·Shuya KasaiKen Itoh
Jun 25, 2020·The FEBS Journal·Shuhei KobayashiYuji Owada
Dec 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jie Wang BJunlian Gu
Dec 15, 2020·Free Radical Biology & Medicine·Yunxia LiuNanhu Quan
Dec 29, 2020·Free Radical Biology & Medicine·Raúl P OliveiraAnabela P Rolo
Oct 29, 2020·Annual Review of Physiology·Myungjin KimJun Hee Lee
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Seung-Hyun RoEdward N Harris
Apr 28, 2020·Experimental Neurology·Ian W Weidling, Russell H Swerdlow
May 8, 2021·Cellular and Molecular Gastroenterology and Hepatology·Zhigang FangX Charlie Dong
Jul 20, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Mackenzie K HerroonIzabela Podgorski
Jul 15, 2021·Journal of Applied Microbiology·Sepideh M AzadYa-Wen He

❮ Previous
Next ❯

Datasets Mentioned

BETA
SRP043021

Methods Mentioned

BETA
RNA-seq
nucleotide exchange
PCR
ChIP
transfection
Assay

Related Concepts

Related Feeds

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis