Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Publication

Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation.

Immunity | 2017

Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7-deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production, and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy-deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation.

Pubmed ID: 28916263 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

Antibodies used in this publication

Associated grants

Agency: Medical Research Council, United Kingdom
Id: MC_UU_00016/5
Agency: Medical Research Council, United Kingdom
Id: G0801073
Agency: Medical Research Council, United Kingdom
Id: MC_UU_12009/5
Agency: Wellcome Trust, United Kingdom
Id: 103830/Z/14/Z
Agency: Medical Research Council, United Kingdom
Id: G0501838

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

BioLegend (tool)

RRID:SCR_001134

Commercial antibody supplier and developer for biomedical research. These products are compatible with use in flow cytometry and mass cytometry, immunoprecipitation and chip, western blotting, immunofluorescence microscopy, and quantitative multiplexing.

View all literature mentions

ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

View all literature mentions

Miltenyi Biotec (tool)

RRID:SCR_008984

An Organization portal, Antibody supplier, Service resource,

View all literature mentions

C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

APC anti-mouse/human CD45R/B220 (antibody)

RRID:AB_312996

This monoclonal targets CD45R

View all literature mentions

PE anti-mouse CD314 (NKG2D) (antibody)

RRID:AB_313659

This monoclonal targets CD314

View all literature mentions

FITC anti-mouse CD326 (Ep-CAM) (antibody)

RRID:AB_1134107

This monoclonal targets CD326

View all literature mentions

PE anti-mouse/human CD11b (antibody)

RRID:AB_312790

This monoclonal targets CD11b

View all literature mentions

APC anti-mouse CD4 (antibody)

RRID:AB_312696

This monoclonal targets CD4

View all literature mentions

APC/Cyanine7 anti-mouse CD117 (c-kit) (antibody)

RRID:AB_2632809

This monoclonal targets CD117

View all literature mentions

Alexa Fluor(R) 488 anti-mouse CD36 (antibody)

RRID:AB_528791

This monoclonal targets CD36

View all literature mentions

APC anti-mouse CD4 (antibody)

RRID:AB_312697

This monoclonal targets CD4

View all literature mentions

APC anti-mouse/human CD45R/B220 (antibody)

RRID:AB_312997

This monoclonal targets CD45R

View all literature mentions

PE anti-mouse/human CD11b (antibody)

RRID:AB_312791

This monoclonal targets CD11b

View all literature mentions

APC/Cyanine7 anti-mouse CD117 (c-kit) (antibody)

RRID:AB_1626278

This monoclonal targets CD117

View all literature mentions

PE anti-mouse CD34 (antibody)

RRID:AB_2629648

This monoclonal targets CD34

View all literature mentions

Mouse G-CSF R/CD114 MAb (Clone 680206) (antibody)

RRID:AB_10890232

This monoclonal targets Mouse G-CSF R/CD114 MAb (Clone 680206)

View all literature mentions

APC anti-mouse CD19 (antibody)

RRID:AB_313646

This monoclonal targets CD19

View all literature mentions

APC anti-mouse CD8a (antibody)

RRID:AB_312751

This monoclonal targets CD8a

View all literature mentions

APC anti-mouse TER-119/Erythroid Cells (antibody)

RRID:AB_313713

This monoclonal targets TER-119

View all literature mentions

PE/Cyanine7 anti-mouse Ly-6G (antibody)

RRID:AB_1877261

This monoclonal targets Ly-6G

View all literature mentions

32Dcl3 (cell line)

RRID:CVCL_0119

Cell line 32Dcl3 is a Factor-dependent cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions

Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

FlowJo (software resource)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

View all literature mentions

GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions