RIPK1 Promotes Energy Sensing by the mTORC1 Pathway

Ayaz Najafov; Hoang Son Luu; Adnan K. Mookhtiar; Lauren Mifflin; Hong guang Xia; Palak P. Amin; Alban Ordureau; Huibing Wang; Junying Yuan

doi:10.1016/j.molcel.2020.11.008

RIPK1 Promotes Energy Sensing by the mTORC1 Pathway

Ayaz Najafov, Hoang Son Luu, Adnan K. Mookhtiar, Lauren Mifflin, Hong guang Xia, Palak P. Amin, Alban Ordureau, Huibing Wang, Junying Yuan

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

RIPK1 scaffold activity is known to have a pro-survival role in TNFα signaling. Najafov et al. discover an unexpected role for RIPK1 scaffold activity in mediating mTORC1 inhibition by AMPK during energetic stress. Mechanistic studies reveal that RIPK1 is involved in regulating TSC2 phosphorylation at Ser1387 by AMPK. Reduced phosphorylation of this site in RIPK1-deficient cells results in a chronically elevated mTORC1 activity and lysosomal dysfunction.

Original language	English (US)
Pages (from-to)	370-385.e7
Journal	Molecular cell
Volume	81
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2020.11.008
State	Published - Jan 21 2021
Externally published	Yes

Keywords

AMPK
CASP8
MLKL
RIPK1
RIPK3
TSC2
lysosome
mTORC1
neonatal lethality

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2020.11.008

Cite this

@article{3ef042b422374ecc981b1c28c5fc15f1,

title = "RIPK1 Promotes Energy Sensing by the mTORC1 Pathway",

abstract = "RIPK1 scaffold activity is known to have a pro-survival role in TNFα signaling. Najafov et al. discover an unexpected role for RIPK1 scaffold activity in mediating mTORC1 inhibition by AMPK during energetic stress. Mechanistic studies reveal that RIPK1 is involved in regulating TSC2 phosphorylation at Ser1387 by AMPK. Reduced phosphorylation of this site in RIPK1-deficient cells results in a chronically elevated mTORC1 activity and lysosomal dysfunction.",

keywords = "AMPK, CASP8, MLKL, RIPK1, RIPK3, TSC2, lysosome, mTORC1, neonatal lethality",

author = "Ayaz Najafov and Luu, {Hoang Son} and Mookhtiar, {Adnan K.} and Lauren Mifflin and Xia, {Hong guang} and Amin, {Palak P.} and Alban Ordureau and Huibing Wang and Junying Yuan",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

month = jan,

day = "21",

doi = "10.1016/j.molcel.2020.11.008",

language = "English (US)",

volume = "81",

pages = "370--385.e7",

journal = "Molecular cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - RIPK1 Promotes Energy Sensing by the mTORC1 Pathway

AU - Najafov, Ayaz

AU - Luu, Hoang Son

AU - Mookhtiar, Adnan K.

AU - Mifflin, Lauren

AU - Xia, Hong guang

AU - Amin, Palak P.

AU - Ordureau, Alban

AU - Wang, Huibing

AU - Yuan, Junying

PY - 2021/1/21

Y1 - 2021/1/21

N2 - RIPK1 scaffold activity is known to have a pro-survival role in TNFα signaling. Najafov et al. discover an unexpected role for RIPK1 scaffold activity in mediating mTORC1 inhibition by AMPK during energetic stress. Mechanistic studies reveal that RIPK1 is involved in regulating TSC2 phosphorylation at Ser1387 by AMPK. Reduced phosphorylation of this site in RIPK1-deficient cells results in a chronically elevated mTORC1 activity and lysosomal dysfunction.

AB - RIPK1 scaffold activity is known to have a pro-survival role in TNFα signaling. Najafov et al. discover an unexpected role for RIPK1 scaffold activity in mediating mTORC1 inhibition by AMPK during energetic stress. Mechanistic studies reveal that RIPK1 is involved in regulating TSC2 phosphorylation at Ser1387 by AMPK. Reduced phosphorylation of this site in RIPK1-deficient cells results in a chronically elevated mTORC1 activity and lysosomal dysfunction.

KW - AMPK

KW - CASP8

KW - MLKL

KW - RIPK1

KW - RIPK3

KW - TSC2

KW - lysosome

KW - mTORC1

KW - neonatal lethality

UR - http://www.scopus.com/inward/record.url?scp=85097801817&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85097801817&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2020.11.008

DO - 10.1016/j.molcel.2020.11.008

M3 - Article

C2 - 33271062

AN - SCOPUS:85097801817

SN - 1097-2765

VL - 81

SP - 370-385.e7

JO - Molecular cell

JF - Molecular cell

IS - 2

ER -

RIPK1 Promotes Energy Sensing by the mTORC1 Pathway

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this