Evidence map›Paper›PMID 40654609›Full record

ArticlebioRxiv : the preprint server for biology2025

Unraveling the Molecular Mechanisms of ABHD5 Membrane Targeting.

Amit Kumar, Matthew Sanders, Huamei Zhang, Li Zhou, Shahnaz Parveen, Christopher V Kelly, James G Granneman, Yu-Ming M Huang

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Amit KumarDepartment of Physics and Astronomy, Wayne State University, Detroit, MI 48201, USA.
Matthew SandersCenter for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, United States.
Huamei ZhangCenter for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, United States.
Li ZhouCenter for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, United States.
Shahnaz ParveenDepartment of Physics and Astronomy, Wayne State University, Detroit, MI 48201, USA.
Christopher V KellyDepartment of Physics and Astronomy, Wayne State University, Detroit, MI 48201, USA.
James G GrannemanCenter for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201, United States.
Yu-Ming M HuangDepartment of Physics and Astronomy, Wayne State University, Detroit, MI 48201, USA.ORCID 0000-0003-3257-6170

Funding

Analysis of Lipolytic Trafficking in Adipocytes.R01DK076629 · NIDDK · WAYNE STATE UNIVERSITY · PI James G Granneman, Christopher V Kelly · 2009 to 2026
$7.1M
Preclinical validation of ABHD5 as a target for treatment of obesity.R01DK105963 · NIDDK · WAYNE STATE UNIVERSITY · PI GRANNEMAN, JAMES G · 2015 to 2018
$2.7M
NIDDK NIH HHS R01 DK076629NIDDK NIH HHS R01 DK105963
6 · The paper itself

Abstract

ABHD5 plays a critical role in lipid metabolism, regulating fatty acid mobilization, skin barrier formation, and phospholipid remodeling. ABHD5 lacks catalytic activity and instead functions as an essential co-regulator of PNPLA enzymes. Understanding how ABHD5 interacts with lipid droplet (LD) and endoplasmic reticulum (ER) membranes is crucial for unraveling its regulatory role in lipid metabolism and identifying potential therapeutic targets for metabolic diseases. While previous studies have modeled ABHD5 structure in solution, its function relies on membrane interactions, requiring a detailed investigation of its binding mechanisms. In this study, we employed multiscale simulations with experimental validation to reveal how ABHD5 interacts with ER and LD. Our findings show that ABHD5 binds membranes through its N-terminus and insertion segment, which subsequently triggers structural changes in the pseudosubstrate pocket and alters lipid distribution. This study also identifies key residues essential for membrane binding, providing potential targets for developing lipid metabolism modulators. These results uncover a previously unrecognized mechanism by which ABHD5 interacts with membranes, offering new insights into lipolysis regulation and potential therapeutic strategies for metabolic diseases.

Indexed as

lipid homeostasismetabolic regulationmolecular dynamicsprotein-membrane interactionα/β-hydrolase domain-containing protein

Identifiers

PMID40654609
PMCPMC12247759

What Socratic 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 Socratic graph.