Mitochondria: sensors and mediators of innate immune receptor signaling

Cloonan, Suzanne M.; Choi, Augustine M.K.

doi:10.1016/j.mib.2013.05.005

Cited by 58 publications

(55 citation statements)

References 103 publications

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“…In the Python heart, we found evidence of activated innate immune signaling, consistent with recent work demonstrating that a failure of cellular control of mitochondria can result in the activation of the inflammasome, Toll-like receptors, stimulator of interferon genes (STING) and mitochondrial antiviral signaling protein (MAVS) (31). Activation of cardiac inflammatory nodes, specifically TLR9, influences mitochondrial cal- cium by inhibition of SERCA2, reducing mitochondrial calcium uptake and ATP synthesis (40).…”

Section: Discussionsupporting

confidence: 87%

Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

Cahill

Leo

Kelly

et al. 2015

Journal of Biological Chemistry

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Background:The C452F mutation in the mitochondrial fission protein Drp1 leads to heart failure through an unknown mechanism. Results: C452F impairs Drp1 disassembly, leading to impaired mitophagy, failed bioenergetics, and inflammation. Conclusion: Drp1-mediated mitochondrial fission is essential for normal cardiac function. Significance: Mutations in mitochondrial quality control proteins are a likely cause of human cardiomyopathy.

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Section: Discussionsupporting

confidence: 87%

Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

Cahill

Leo

Kelly

et al. 2015

Journal of Biological Chemistry

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“…However, LPSstimulated TCAIM-BMDCs were characterized by a reduced Ca Mitochondria play an important and decisive role in cell signaling. Especially their role in immune cell signaling has gained much attention in recent years (24,25). Apart from regulating apoptosis, mitochondrial release of ROS is instrumental for redoxsensitive signaling pathways such as activation of MAP kinases, NF-kB, and AP1 as well as mitochondria are indispensable for Ca 2+ signaling (22,(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

TCAIM Decreases T Cell Priming Capacity of Dendritic Cells by Inhibiting TLR-Induced Ca2+ Influx and IL-2 Production

Vogel

Schlickeiser

Jürchott

et al. 2015

The Journal of Immunology

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We previously showed that the T cell activation inhibitor, mitochondrial (Tcaim) is highly expressed in grafts of tolerance-developing transplant recipients and that the encoded protein is localized within mitochondria. In this study, we show that CD11c+ dendritic cells (DCs), as main producers of TCAIM, downregulate Tcaim expression after LPS stimulation or in vivo alloantigen challenge. LPS-stimulated TCAIM-overexpressing bone marrow–derived DC (BMDCs) have a reduced capacity to induce proliferation of and cytokine expression by cocultured allogeneic T cells; this is not due to diminished upregulation of MHC or costimulatory molecules. Transcriptional profiling also revealed normal LPS-mediated upregulation of the majority of genes involved in TLR signaling. However, TCAIM BMDCs did not induce Il2 mRNA expression upon LPS stimulation in comparison with Control-BMDCs. In addition, TCAIM overexpression abolished LPS-mediated Ca2+ influx and mitochondrial reactive oxygen species formation. Addition of IL-2 to BMDC–T cell cocultures restored the priming capacity of TCAIM BMDCs for cocultured allogeneic CD8+ T cells. Furthermore, BMDCs of IL-2–deficient mice showed similarly abolished LPS-induced T cell priming as TCAIM-overexpressing wild type BMDCs. Thus, TCAIM interferes with TLR4 signaling in BMDCs and subsequently impairs their T cell priming capacity, which supports its role for tolerance induction.

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“…Mitochondria are essential organelles that produce ATP through oxidative phosphorylation and participate in a number of other cellular processes (Cloonan and Choi, 2013;Tait and Green, 2010;Vyas et al, 2016). Although mitochondria have their own genomes, the vast majority of mitochondrial proteins are encoded in the nucleus (∼1500) (Meisinger et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality

2017

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Mitochondrial dysfunction can cause female infertility. An important unresolved issue is the extent to which incompatibility between mitochondrial and nuclear genomes contributes to female infertility. It has previously been shown that a mitochondrial haplotype from D. simulans (simw 501) is incompatible with a nuclear genome from the D. melanogaster strain Oregon-R (OreR), resulting in impaired development, which was enhanced at higher temperature. This mitonuclear incompatibility is between alleles of the nuclear-encoded mitochondrial tyrosyl-tRNA synthetase (Aatm) and the mitochondrialencoded tyrosyl-tRNA that it aminoacylates. Here, we show that this mito-nuclear incompatibility causes a severe temperature-sensitive female infertility. The OreR nuclear genome contributed to death of ovarian germline stem cells and reduced egg production, which was further enhanced by the incompatibility with simw 501 mitochondria. Mito-nuclear incompatibility also resulted in aberrant egg morphology and a maternal-effect on embryonic chromosome segregation and survival, which was completely dependent on the temperature and mito-nuclear genotype of the mother. Our findings show that maternal mito-nuclear incompatibility during Drosophila oogenesis has severe consequences for egg production and embryonic survival, with important broader relevance to human female infertility and mitochondrial replacement therapy.

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Mitochondria: sensors and mediators of innate immune receptor signaling

Cited by 58 publications

References 103 publications

Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

Resistance of Dynamin-related Protein 1 Oligomers to Disassembly Impairs Mitophagy, Resulting in Myocardial Inflammation and Heart Failure

TCAIM Decreases T Cell Priming Capacity of Dendritic Cells by Inhibiting TLR-Induced Ca2+ Influx and IL-2 Production

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality

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