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The Mitochondrial RNA Granule is Necessary for Parkinsonism-Associated Metal Toxicity

ABSTRACT: We measured the proteome of wild type HAP1 cells and cells mutant for the manganese transporter SLC30A10, PARK2, and the ADP-ATP mitochondrial translocator SLC25A4.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Parkinson's Disease

SUBMITTER: Victor Faundez

LAB HEAD: Victor Faundez

PROVIDER: PXD030502 | Pride | 2023-03-11

REPOSITORIES: Pride

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			Action	DRS
	Experiment Emory 7146_A from MSB7146AsRP2Pool_01 +11 others.mzid.gz	Mzid
	Experiment Emory 7146_A from MSB7146AsRP2Pool_01 +11 others.mzid_Experiment_Emory_7146_A_from_MSB7146AsRP2Pool_01_+11_others.MGF	Mzid
	Experiment Emory 7146_B from MSB7146BsRP2Pool_01 +11 others.mzid.gz	Mzid
	Experiment Emory 7146_B from MSB7146BsRP2Pool_01 +11 others.mzid_Experiment_Emory_7146_B_from_MSB7146BsRP2Pool_01_+11_others.MGF	Mzid
	MSB7146AsRP2Pool_01.raw	Raw

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Publications

The mitochondrial RNA granule modulates manganese-dependent cell toxicity.

Werner E E Gokhale A A Ackert M M Xu C C Wen Z Z Roberts A M AM Roberts B R BR Vrailas-Mortimer A A Crocker A A Faundez V V

Molecular biology of the cell 20220803 12

Prolonged manganese exposure causes manganism, a neurodegenerative movement disorder. The identity of adaptive and nonadaptive cellular processes targeted by manganese remains mostly unexplored. Here we study mechanisms engaged by manganese in genetic cellular models known to increase susceptibility to manganese exposure, the plasma membrane manganese efflux transporter SLC30A10 and the mitochondrial Parkinson's gene PARK2. We found that SLC30A10 and PARK2 mutations as well as manganese exposure ...[more]

PMID: 35921164

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The Mitochondrial RNA Granule is Necessary for Parkinsonism-Associated Metal Toxicity

Project description:We report RNAseq profiles of human cell lines with deletions of the SLC30A10 gene or the PARK2 gene.

2022-11-09 | GSE192392 | GEO

The Mitochondrial RNA Granule is Necessary for Parkinsonism-Associated Metal Toxicity

Project description:The Mitochondrial RNA Granule is Necessary for Parkinsonism-Associated Metal Toxicity

| PRJNA791334 | ENA

Decoding the global transcriptomic profile under extreme manganese toxicity

Project description:To achieve extreme manganese stress, we used DmntP E. coli strain. We identified the pathways that are altered under manganese stress. Mainly, manganese altered the metabolism of iron in the cell. Therefore, we have shown that iron supplementation mitigates manganese toxicity. Overall, our data explains the basis of manganism in higher organisms.

2017-11-01 | GSE88906 | GEO

The hierarchy of transition metal homeostasis: Iron controls manganese accumulation in a unicellular cyanobacterium.

Project description:Iron and manganese are part of a small group of transition metals required for photosynthetic electron transport. Here, we present evidence for a functional link between iron and manganese homeostasis. In the unicellular cyanobacterium, Synechocystis sp. PCC 6803 Fe and Mn deprivation resulted in distinct modifications of the function of the photosynthetic apparatus. For example, iron limitation modifies the rate of QA re-oxidation in photosystem II, a complex that contains more Mn than Fe. The intracellular elemental quotas of Fe and Mn are also linked. Fe limitation reduces the intracellular Mn quota. Mn limitation did not exert a reciprocal effect on Fe quotas. Microarray analysis comparing Mn and Fe limitation revealed a stark difference in the extent of the transcriptional response to the two limiting conditions, reflective of the physiological data. The effects of Fe limitation on the transcriptional network are widespread while the effects on Mn limitation are highly specific. Our analysis also revealed an overlap in the transcriptional response of specific Fe and Mn transporters. This overlap provides a framework for explaining Fe limitation induced changes in Mn quotas. Fe transporters can serve as a low affinity Mn transport system. Under iron limitation the specificity of the Fe transport system changes, making it a less efficient Mn transport system. We monitored the gene expression of Synechocystis PCC6083 at standard conditions and after 2 days of iron limitation (0Fe), manganese limitation (0Mn) and combined iron and manganese limitation (0Fe0Mn). Each timepoint and condition was sampled in triplicates. Due to strong deviations in one of the three repeats for the 0Mn and 0Fe0Mn conditions, the corresponding replicates were excluded from further analysis.

2013-06-29 | E-GEOD-48416 | biostudies-arrayexpress

Agilent 244K aCGH data for colon cancer samples

Project description:Mutation of the gene PARK2 is the most common cause of early-onset Parkinson's Disease (PD)1,2. PARK2 encodes a gene product with E3 ubiquitin ligase activity3. In a search for multisite tumor suppressors, we identified PARK2 as a frequently targeted gene on chromosome 6q25.2-q27 in cancer. Here, we describe inactivating somatic mutations and frequent intragenic deletions of PARK2 in human malignancies. The PARK2 mutations in cancer occur in the same domains, and sometimes, at the same residues as the germline mutations causing familial PD. Cancer-specific mutations abrogate the growth suppressive effects of PARK2. PARK2 mutations in cancer decrease the gene product's E3 ligase activity, compromising its ability to ubiquitinate cyclin E and resulting in mitotic instability. These data strongly point to PARK2 as a tumor suppressor on 6q25.2-q27. PARK2, a gene that causes neuronal dysfunction when mutated in the germline, may instead contribute to oncogenesis when altered in non-neuronal somatic cells. Human colorectal samples were profiled on Agilent 244K aCGH arrays per manufacturer's instructions. Pooled reference normal DNA was used as the reference.

2010-06-22 | E-GEOD-18638 | biostudies-arrayexpress

PARK2 knockdown in 2 glioma cell lines

Project description:The PARK2 gene was knocked down using 2 independent siRNAs in SNB19 and SF539 cell lines A non-targeted scramble siRNA was used as the control. Scramble, PARK2 siRNA#1 or PARK2 siRNA#2 was transfected into each cell line, in duplicate, and RNA analyzed using the Affymetrix U133A 2.0 platform.

2014-04-11 | E-GEOD-50864 | biostudies-arrayexpress

B. japonicum USDA110 low manganese vs. high manganese

Project description:Transcriptional profiling of B. japonicum manganese responsive cells and mur mutant responsive cells 3 independent biological materials were prepared for Wt manganese deplete, replete cultured cells and mur mutant manganese replete cultured cells

2011-08-24 | E-GEOD-30932 | biostudies-arrayexpress

Next-generation sequencing facilitates metal homeostasis and intoxication studies

Project description:Purpose: Analyze transcriptome changes in response to metal treatment in wildtype and sensitized genetic backgrounds. Methods: Zinc or manganese chloride supplementation of wildtype or mutant Drosophila S2R+ cultured cells, followed by RNA extraction. Results: Zinc chloride supplementation induces transcriptional responses in wildtype, ia-2 mutant, and ZnT63C mutant cells. Conclusions: Wildtype S2R+ cells have a transcriptional response to mild zinc chloride supplementation and the zinc response is greater (in degree and in number of genes) in genetically sensitized cell backgrounds that perturb zinc mobilization.

2017-06-30 | GSE99332 | GEO

Agilent 244K aCGH data for colon cancer samples

2009-10-21 | GSE18638 | GEO

Expression data from PARK2 overexpression in U251 cells

Project description:PARK2 (PARKIN) is an E3 ubiquitin ligase whose dysfunction has been associated with the progression of Parkinsonism and human malignancies, and its role in cancer remains to be explored. In this study, we investigated its role in glioma. We used microarrays to detail the global programme of gene expression upon PARK2 overexpression in U251 cells U251 cells with PARK2 overexpression or control (GFP) were subjected for RNA extraction and hybridization on Affymetrix microarrays.

2014-10-03 | E-GEOD-61973 | biostudies-arrayexpress

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