Evidence map›Paper›PMID 37689067›Full record

ArticleCell reports2023

The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.

Rowan A Boyd, Saurav Majumder, Johnny Stiban, Grace Mavodza, Alexandra J Straus, Sachin K Kempelingaiah, Varun Reddy, Yusuf A Hannun, Lina M Obeid, Can E Senkal

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 25 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

10 authors at 3 institutions in 2 countries.

Rowan A BoydDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA.
Saurav MajumderDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA.
Johnny StibanDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA; Department of Biology and Biochemistry, Birzeit University, Ramallah, Palestine.
Grace MavodzaDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA.
Alexandra J StrausDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA.
Sachin K KempelingaiahDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA.
Varun ReddyDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.
Yusuf A HannunDepartment of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA; Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA.
Lina M ObeidStony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11794, USA; Northport Veterans Affairs Medical Center, Northport, NY 11768, USA.
Can E SenkalDepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23398, USA; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23398, USA. Electronic address: can.senkal@vcuhealth.org.
Virginia Commonwealth University · USStony Brook University · USStony Brook Medicine · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0M
Sphingolipids in Cancer Therapy and AngiogenesisP01CA097132 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Daniel Canals · 2003 to 2026
$30.8M
Neutral Sphingomyelinases and Bioactive CeramidesR35GM118128 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI HANNUN, YUSUF AWNI · 2016 to 2025
$7.9M
Ceramide Activated Protein PhosphatasesR01CA218678 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI YUSUF AWNI HANNUN · 2018 to 2026
$3.4M
Regulation of Ceramide Synthase by Protein-Protein InteractionR37CA239532 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SENKAL, CAN EMRE · 2019 to 2025
$2.4M
NCI NIH HHS P01 CA097132NCI NIH HHS P30 CA016059NCI NIH HHS R01 CA218678NCI NIH HHS R37 CA239532NIGMS NIH HHS R35 GM118128
6 · The paper itself

Abstract

Sphingolipids have key functions in membrane structure and cellular signaling. Ceramide is the central molecule of the sphingolipid metabolism and is generated by ceramide synthases (CerS) in the de novo pathway. Despite their critical function, mechanisms regulating CerS remain largely unknown. Using an unbiased proteomics approach, we find that the small heat shock protein 27 (Hsp27) interacts specifically with CerS1 but not other CerS. Functionally, our data show that Hsp27 acts as an endogenous inhibitor of CerS1. Wild-type Hsp27, but not a mutant deficient in CerS1 binding, inhibits CerS1 activity. Additionally, silencing of Hsp27 enhances CerS1-generated ceramide accumulation in cells. Moreover, phosphorylation of Hsp27 modulates Hsp27-CerS1 interaction and CerS1 activity in acute stress-response conditions. Biologically, we show that Hsp27 knockdown impedes mitochondrial function and induces lethal mitophagy in a CerS1-dependent manner. Overall, we identify an important mode of CerS1 regulation and CerS1-mediated mitophagy through protein-protein interaction with Hsp27.

Indexed as

CeramidesHSP27 Heat-Shock ProteinsHeat-Shock ProteinsHumansMitochondriaMitophagyMolecular ChaperonesSphingolipidsCeramidesHeat-Shock ProteinsHSP27 Heat-Shock ProteinsHSPB1 protein, humanMolecular ChaperonesSphingolipidsC18-ceramideceramideceramide synthaseCerS1CP: Molecular biologyHsp27mitophagysphingolipids

Identifiers

PMID37689067
PMCPMC10591768
OpenAlexW4386563589

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.