Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming
Por:
B. PALACIOS, R. VILLARES, P. LUCAS, J. RODRIGUEZ-FRADE, A. CAYUELA, J. PICCIRILLO, M. LOMBARDIA, D. GESTOSO, M. FERNANDEZ-GARCIA, C. RISCO, C. BARBAS, F. CORRALES, C. SORZANO, N. MARTINEZ-MARTIN, J. CONESA, F. IBORRA and M. MELLADO
Publicada:
5 jul 2023
Resumen:
IntroductionMacrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming. MethodsHere we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy. ResultsWe demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-Mo) by functioning as a metabolic modulator. We found that exogenous treatment of GM-Mo with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-Mo. Moreover, GH treatment of GM-Mo augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae. ConclusionsOur data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases.
Filiaciones:
B. PALACIOS:
CSIC, Natl Ctr Biotechnol, Dept Immunol & Oncol, Madrid, Spain
R. VILLARES:
CSIC, Natl Ctr Biotechnol, Dept Immunol & Oncol, Madrid, Spain
P. LUCAS:
CSIC, Natl Ctr Biotechnol, Dept Immunol & Oncol, Madrid, Spain
J. RODRIGUEZ-FRADE:
CSIC, Natl Ctr Biotechnol, Dept Immunol & Oncol, Madrid, Spain
A. CAYUELA:
CSIC, Natl Ctr Biotechnol, Biocomp Unit, Madrid, Spain
J. PICCIRILLO:
Natl Ctr Biotechnol, Spanish Natl Res Council CSIC, Dept Macromol Struct, Madrid, Spain
M. LOMBARDIA:
CSIC, Natl Ctr Biotechnol, Funct Prote Lab, Madrid, Spain
D. GESTOSO:
Natl Ctr Biotechnol, Spanish Natl Res Council CSIC, Dept Macromol Struct, Madrid, Spain
M. FERNANDEZ-GARCIA:
Univ San Pablo CEU, Ctr Univ Studies CEU Univ, Pharm Fac, Metabol & Bioanal Ctr CEMBIO, Boadilla Del Monte, Spain
Univ San Pablo CEU, Ctr Univ Studies CEU Univ, Med Fac, Dept Basic Med Sci, Boadilla Del Monte, Spain
C. RISCO:
Natl Ctr Biotechnol, Spanish Natl Res Council CSIC, Dept Macromol Struct, Madrid, Spain
C. BARBAS:
Univ San Pablo CEU, Ctr Univ Studies CEU Univ, Pharm Fac, Metabol & Bioanal Ctr CEMBIO, Boadilla Del Monte, Spain
F. CORRALES:
CSIC, Natl Ctr Biotechnol, Funct Prote Lab, Madrid, Spain
C. SORZANO:
CSIC, Natl Ctr Biotechnol, Biocomp Unit, Madrid, Spain
N. MARTINEZ-MARTIN:
Autonomus Univ Madrid UAM, Spanish Natl Res Council CSIC, Ctr Biol Mol Severo Ochoa, Tissue & Organ Homeostasis Program, Madrid, Spain
J. CONESA:
Natl Ctr Biotechnol, Spanish Natl Res Council CSIC, Dept Macromol Struct, Madrid, Spain
:
Biomed Inst Valencia, Associated Unit, Principe Felipe Res Ctr, Valencia, Spain
M. MELLADO:
CSIC, Natl Ctr Biotechnol, Dept Immunol & Oncol, Madrid, Spain
Green Published, Green Submitted, gold
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