SIRT2 regulates mitochondrial dynamics and reprogramming via MEK1-ERK-DRP1 and AKT1-DRP1 axes
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved..
During somatic reprogramming, cellular energy metabolism fundamentally switches from predominantly mitochondrial oxidative phosphorylation toward glycolysis. This metabolic reprogramming, also called the Warburg effect, is critical for the induction of pluripotency, but its molecular mechanisms remain poorly defined. Notably, SIRT2 is consistently downregulated during the reprogramming process and regulates glycolytic switch. Here, we report that downregulation of SIRT2 increases acetylation of mitogen-activated protein kinase (MAPK) kinase-1 (MEK1) at Lys175, resulting in activation of extracellular signal-regulated kinases (ERKs) and subsequent activation of the pro-fission factor dynamin-related protein 1 (DRP1). In parallel, downregulation of SIRT2 hyperacetylates the serine/threonine protein kinase AKT1 at Lys20 in a non-canonical way, activating DRP1 and metabolic reprogramming. Together, our study identified two axes, SIRT2-MEK1-ERK-DRP1 and SIRT2-AKT1-DRP1, that critically link mitochondrial dynamics and oxidative phosphorylation to the somatic reprogramming process. These upstream signals, together with SIRT2's role in glycolytic switching, may underlie the Warburg effect observed in human somatic cell reprogramming.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:37 |
|---|---|
| Enthalten in: |
Cell reports - 37(2021), 13 vom: 28. Dez., Seite 110155 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Cha, Young [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.02.2022 Date Revised 15.02.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.celrep.2021.110155 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM335012299 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM335012299 | ||
| 003 | DE-627 | ||
| 005 | 20231226204031.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.celrep.2021.110155 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1116.xml |
| 035 | |a (DE-627)NLM335012299 | ||
| 035 | |a (NLM)34965411 | ||
| 035 | |a (PII)S2211-1247(21)01651-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Cha, Young |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SIRT2 regulates mitochondrial dynamics and reprogramming via MEK1-ERK-DRP1 and AKT1-DRP1 axes |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.02.2022 | ||
| 500 | |a Date Revised 15.02.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a During somatic reprogramming, cellular energy metabolism fundamentally switches from predominantly mitochondrial oxidative phosphorylation toward glycolysis. This metabolic reprogramming, also called the Warburg effect, is critical for the induction of pluripotency, but its molecular mechanisms remain poorly defined. Notably, SIRT2 is consistently downregulated during the reprogramming process and regulates glycolytic switch. Here, we report that downregulation of SIRT2 increases acetylation of mitogen-activated protein kinase (MAPK) kinase-1 (MEK1) at Lys175, resulting in activation of extracellular signal-regulated kinases (ERKs) and subsequent activation of the pro-fission factor dynamin-related protein 1 (DRP1). In parallel, downregulation of SIRT2 hyperacetylates the serine/threonine protein kinase AKT1 at Lys20 in a non-canonical way, activating DRP1 and metabolic reprogramming. Together, our study identified two axes, SIRT2-MEK1-ERK-DRP1 and SIRT2-AKT1-DRP1, that critically link mitochondrial dynamics and oxidative phosphorylation to the somatic reprogramming process. These upstream signals, together with SIRT2's role in glycolytic switching, may underlie the Warburg effect observed in human somatic cell reprogramming | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AKT1 | |
| 650 | 4 | |a DRP1 | |
| 650 | 4 | |a MEK1-ERK axis | |
| 650 | 4 | |a OXPHOS | |
| 650 | 4 | |a SIRT2 | |
| 650 | 4 | |a Warburg-like effect | |
| 650 | 4 | |a human somatic cell reprogramming | |
| 650 | 4 | |a induced pluripotent stem cells | |
| 650 | 4 | |a metabolic reprogramming | |
| 650 | 4 | |a mitochondrial remodeling | |
| 650 | 7 | |a AKT1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a MAPK1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a MAPK3 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a Mitogen-Activated Protein Kinase 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a Mitogen-Activated Protein Kinase 3 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.24 |2 NLM | |
| 650 | 7 | |a MAP Kinase Kinase 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.12.2 |2 NLM | |
| 650 | 7 | |a MAP2K1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.12.2 |2 NLM | |
| 650 | 7 | |a SIRT2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 650 | 7 | |a Sirtuin 2 |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 650 | 7 | |a DNM1L protein, human |2 NLM | |
| 650 | 7 | |a EC 3.6.5.5 |2 NLM | |
| 650 | 7 | |a Dynamins |2 NLM | |
| 650 | 7 | |a EC 3.6.5.5 |2 NLM | |
| 700 | 1 | |a Kim, Taewoo |e verfasserin |4 aut | |
| 700 | 1 | |a Jeon, Jeha |e verfasserin |4 aut | |
| 700 | 1 | |a Jang, Yongwoo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Patrick B |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Leblanc, Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Bruce M |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kwang-Soo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell reports |d 2012 |g 37(2021), 13 vom: 28. Dez., Seite 110155 |w (DE-627)NLM217067492 |x 2211-1247 |7 nnns |
| 773 | 1 | 8 | |g volume:37 |g year:2021 |g number:13 |g day:28 |g month:12 |g pages:110155 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.celrep.2021.110155 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 37 |j 2021 |e 13 |b 28 |c 12 |h 110155 | ||