Dataset Information

A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Molecular Determinants in Redox Homeostasis and NF-κB Signaling

ABSTRACT: Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs), however, the discovery of molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using 109 affinity-purified mitochondrial fractions isolated from 13 epitope-tagged human ND-linked MPs in HEK293 cells coupled with mass spectrometry (MS), we report a high-confidence MP network involving 1,964 interactions among 772 proteins (>90% previously unreported). Nearly half of these interactions were confirmed in differentiated neuronal cells by primary antibody immunoprecipitation and MS, with many linked to NDs and autism. We show that the SOD1-PRDX5 interaction, critical for mitochondrial redox homeostasis, can be perturbed by amyotrophic lateral sclerosis-linked variants, and establish a new functional role for ND-linked factors coupled with IκBε in NF-kB activation. Our results identify new mechanisms for MPs with direct consequences for human disease, and expands the interaction landscape of human mitochondria

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Sadhna Phanse

LAB HEAD: Dr. Mohan Babu

PROVIDER: PXD006690 | Pride | 2017-12-05

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	FINV_uniprot_sprot_human_BSA_TRY_BCN_GFP_TEV_062911.fasta	Fasta
	GR121228_OT_BL0223_4_VDAC1_FLAG_DIGITONIN_NH4OH_HEK293_HUMAN.mzXML	Mzxml
	GR121228_OT_BL0223_4_VDAC1_FLAG_DIGITONIN_NH4OH_HEK293_HUMAN.mzXML_dta.tar.bz2	Mzxml
	GR121228_OT_BL0223_4_VDAC1_FLAG_DIGITONIN_NH4OH_HEK293_HUMAN.mzXML_out.tar.bz2	Mzxml
	GR121228_OT_BL0225_4_CDC2_FLAG_DIGITONIN_NH4OH_HEK293_HUMAN.mzXML	Mzxml

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A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling.

Malty Ramy H RH Aoki Hiroyuki H Kumar Ashwani A Phanse Sadhna S Amin Shahreen S Zhang Qingzhou Q Minic Zoran Z Goebels Florian F Musso Gabriel G Wu Zhuoran Z Abou-Tok Hosam H Meyer Michael M Deineko Viktor V Kassir Sandy S Sidhu Vishaldeep V Jessulat Matthew M Scott Nichollas E NE Xiong Xuejian X Vlasblom James J Prasad Bhanu B Foster Leonard J LJ Alberio Tiziana T Garavaglia Barbara B Yu Haiyuan H Bader Gary D GD Nakamura Ken K Parkinson John J Babu Mohan M

Cell systems 20171108 6

Mitochondrial protein (MP) dysfunction has been linked to neurodegenerative disorders (NDs); however, the discovery of the molecular mechanisms underlying NDs has been impeded by the limited characterization of interactions governing MP function. Here, using mass spectrometry (MS)-based analysis of 210 affinity-purified mitochondrial (mt) fractions isolated from 27 epitope-tagged human ND-linked MPs in HEK293 cells, we report a high-confidence MP network including 1,964 interactions among 772 pr ...[more]

PMID: 29128334

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