Proximity-labeling chemoproteomics defines the subcellular cysteinome and inflammation- responsive mitochondrial redoxome

被引：16

作者：

Yan, Tianyang ^{[1
,2
]}

Julio, Ashley R. ^{[1
,2
]}

Villanueva, Miranda ^{[1
,4
]}

Jones, Anthony E. ^{[3
]}

Ball, Andrea B. ^{[3
]}

Boatner, Lisa M. ^{[1
,2
]}

Turmon, Alexandra C. ^{[1
,2
]}

Nguyen, Kaitlyn B. ^{[3
]}

Yen, Stephanie L. ^{[1
]}

Desai, Heta S. ^{[1
,4
]}

Divakaruni, Ajit S. ^{[3
]}

Backus, Keriann M. ^{[1
,2
,4
,5
,6
,7
]}

机构：

[1] UCLA, David Geffen Sch Med, Biol Chem Dept, Los Angeles, CA 90095 USA

[2] UCLA, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[3] UCLA, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[4] UCLA, Mol Biol Inst, Los Angeles, CA 90095 USA

[5] UCLA, DOE Inst Genom & Prote, Los Angeles, CA 90095 USA

[6] UCLA, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA

[7] UCLA, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell R, Los Angeles, CA 90095 USA

来源：

CELL CHEMICAL BIOLOGY | 2023年 / 30卷 / 07期

基金：

美国国家卫生研究院;

关键词：

OXIDE SYNTHASE GENE; OXIDATIVE STRESS; INTERFERON-GAMMA; PROTEIN; CYCLOHEXIMIDE; THIOREDOXIN; MACROPHAGES; METABOLISM; MECHANISMS; REVEALS;

D O I：

10.1016/j.chembiol.2023.06.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proteinaceous cysteines function as essential sensors of cellular redox state. Consequently, defining the cysteine redoxome is a key challenge for functional proteomic studies. While proteome-wide inventories of cysteine oxidation state are readily achieved using established, widely adopted proteomic methods such as OxICAT, Biotin Switch, and SP3-Rox, these methods typically assay bulk proteomes and therefore fail to capture protein localization-dependent oxidative modifications. Here we establish the local cysteine capture (Cys-LoC) and local cysteine oxidation (Cys-LOx) methods, which together yield compartment-spe-cific cysteine capture and quantitation of cysteine oxidation state. Benchmarking of the Cys-LoC method across a panel of subcellular compartments revealed more than 3,500 cysteines not previously captured by whole-cell proteomic analysis. Application of the Cys-LOx method to LPS-stimulated immortalized murine bone marrow-derived macrophages (iBMDM), revealed previously unidentified, mitochondrially localized cysteine oxidative modifications upon pro-inflammatory activation, including those associated with oxidative mitochondrial metabolism.

引用

页码：811 / +

页数：25