Dataset Information

Mitochondrial dysfunction caused by bacterial outer membranes vesicles activates intrinsic apoptosis and inflammation

ABSTRACT: Sensing of microbes activates the immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondria activity by delivering toxins via outer membrane vesicles (OMVs). How innate immune cells respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages induce mitochondrial apoptosis and the NLRP3 inflammasome in response OMVs. Macrophages treated with OMVs and toxins that cause mitochondria dysfunction cease host protein translation which depletes pro-survival BCL-2 family member, MCL-1, and induces BAK-dependent mitochondrial apoptosis. Mitochondrial apoptosis and potassium ion efflux activate the NLRP3 inflammasome after OMV exposure. Importantly, mitochondrial apoptosis modulates IL-1 serum levels in response to OMVs. Our data highlight how innate immune cells sense infections by monitoring mitochondrial health.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Cheng Huang

LAB HEAD: Thomas Naderer

PROVIDER: PXD018563 | Pride | 2020-07-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Allproteins_qvaluesparse.xls	Xls
	Allproteins_qvlaue.xlsx	Xlsx
	F1CH20180530_OMV1_375_675.raw	Raw
	F1CH20180530_OMV1_375_975.htrms	Other
	F1CH20180530_OMV1_675_975.raw	Raw

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Publications

Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation.

Deo Pankaj P Chow Seong H SH Han Mei-Ling ML Speir Mary M Huang Cheng C Schittenhelm Ralf B RB Dhital Subhash S Emery Jack J Li Jian J Kile Benjamin T BT Vince James E JE Lawlor Kate E KE Naderer Thomas T

Nature microbiology 20200817 11

Sensing of microbes activates the innate immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondrial activity by delivering toxins via outer membrane vesicles (OMVs). How macrophages respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages exposed to OMVs from Neisseria gonorrhoeae, uropathogenic Escherichia coli and Pseudomonas aeruginosa induce mitochondrial apoptosis and NLRP3 inflammasome activation. O ...[more]

PMID: 32807891

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