Quantitative proteomics reveals the induction of mitophagy in tumor necrosis factor-α-activated (TNFα) macrophages
| Autor: | Olivier Caron-Lizotte, Michel Desjardins, Christina Bell, Magali Chemali, Pierre Thibault, Jonathan Boulais, Luc English |
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| Rok vydání: | 2013 |
| Předmět: |
Proteomics
Proteome Antigen presentation Down-Regulation Phospholipases A2 Cytosolic Biology Major histocompatibility complex Biochemistry Analytical Chemistry Cell Line Mitochondrial Proteins Mice Immune system Antigen Mitophagy MHC class I Autophagy Animals Protein Interaction Maps Antigens Molecular Biology Antigen Presentation Tumor Necrosis Factor-alpha Macrophages Research Histocompatibility Antigens Class I Computational Biology Membrane Proteins Macrophage Activation Acquired immune system Cell biology Mitochondria biology.protein Tumor necrosis factor alpha |
| Zdroj: | Molecularcellular proteomics : MCP. 12(9) |
| ISSN: | 1535-9484 |
| Popis: | Macrophages play an important role in innate and adaptive immunity as professional phagocytes capable of internalizing and degrading pathogens to derive antigens for presentation to T cells. They also produce pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) that mediate local and systemic responses and direct the development of adaptive immunity. The present work describes the use of label-free quantitative proteomics to profile the dynamic changes of proteins from resting and TNF-α-activated mouse macrophages. These analyses revealed that TNF-α activation of macrophages led to the down-regulation of mitochondrial proteins and the differential regulation of several proteins involved in vesicle trafficking and immune response. Importantly, we found that the down-regulation of mitochondria proteins occurred through mitophagy and was specific to TNF-α, as other cytokines such as IL-1β and IFN-γ had no effect on mitochondria degradation. Furthermore, using a novel antigen presentation system, we observed that the induction of mitophagy by TNF-α enabled the processing and presentation of mitochondrial antigens at the cell surface by MHC class I molecules. These findings highlight an unsuspected role of TNF-α in mitophagy and expanded our understanding of the mechanisms responsible for MHC presentation of self-antigens. |
| Databáze: | OpenAIRE |
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