Evidence map›Paper›PMID 28988886›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2018

The ceramide activated protein phosphatase Sit4 impairs sphingolipid dynamics, mitochondrial function and lifespan in a yeast model of Niemann-Pick type C1.

Rita Vilaça, Ivo Barros, Nabil Matmati, Elísio Silva, Telma Martins, Vítor Teixeira, Yusuf A Hannun, Vítor Costa

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta. Molecular basis of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Rita VilaçaInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Ivo BarrosInstituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Nabil MatmatiStony Brook Cancer Center, Stony Brook University, Health Science Center, Stony Brook, NY, USA.
Elísio SilvaInstituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Telma MartinsInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Vítor TeixeiraInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
Yusuf A HannunStony Brook Cancer Center, Stony Brook University, Health Science Center, Stony Brook, NY, USA.
Vítor CostaInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Departamento de Biologia Molecular, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. Electronic address: vcosta@ibmc.up.pt.
Universidade do Porto · PTStony Brook University · US

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
THE ROLE OF LACTOSYLCERAMIDE IN RENAL AGING AND DISEASEP20RR017677 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MAO, CUNGUI · 2002 to 2011
$23.4M
Neutral Sphingomyelinases and Bioactive CeramidesR35GM118128 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2016 to 2025
$7.9M
CERAMIDE ACTIVATED PROTEIN PHOSPHATASESR01CA087584 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2000 to 2015
$4.2M
Modeling and Analysis of Yeast Sphingolipid MetabolismR01GM063265 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2001 to 2013
$3.4M
NCI NIH HHS P30 CA138313NCI NIH HHS R01 CA087584NCRR NIH HHS P20 RR017677NIGMS NIH HHS R01 GM063265NIGMS NIH HHS R35 GM118128
6 · The paper itself

Abstract

The Niemann-Pick type C is a rare neurodegenerative disease that results from loss-of-function point mutations in NPC1 or NPC2, which affect the homeostasis of sphingolipids and sterols in human cells. We have previously shown that yeast lacking Ncr1, the orthologue of human NPC1 protein, display a premature ageing phenotype and higher sensitivity to oxidative stress associated with mitochondrial dysfunctions and accumulation of long chain bases. In this study, a lipidomic analysis revealed specific changes in the levels of ceramide species in ncr1Δ cells, including decreases in dihydroceramides and increases in phytoceramides. Moreover, the activation of Sit4, a ceramide-activated protein phosphatase, increased in ncr1Δ cells. Deletion of SIT4 or CDC55, its regulatory subunit, increased the chronological lifespan and hydrogen peroxide resistance of ncr1Δ cells and suppressed its mitochondrial defects. Notably, Sch9 and Pkh1-mediated phosphorylation of Sch9 decreased significantly in ncr1Δsit4Δ cells. These results suggest that phytoceramide accumulation and Sit4-dependent signaling mediate the mitochondrial dysfunction and shortened lifespan in the yeast model of Niemann-Pick type C1, in part through modulation of the Pkh1-Sch9 pathway.

Indexed as

3-Phosphoinositide-Dependent Protein KinasesHumansLipid MetabolismMitochondriaMitochondrial DynamicsModels, BiologicalNiemann-Pick Disease, Type COrganisms, Genetically ModifiedProtein Phosphatase 2Protein Serine-Threonine KinasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionSphingolipids3-Phosphoinositide-Dependent Protein KinasesPKH1 protein, S cerevisiaeProtein Phosphatase 2Protein Serine-Threonine KinasesSaccharomyces cerevisiae ProteinsSCH9 protein, S cerevisiaeSIT4 protein, S cerevisiaeSphingolipidsCeramideMitochondriaNiemann-Pick type CSch9Sit4Sphingolipid signaling

Identifiers

PMID28988886
PMCPMC5705342
OpenAlexW2761841619

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.