PXD039382

PXD039382 is an original dataset announced via ProteomeXchange.

Title	Systematic investigation of dose-dependent protein thermal stability changes to uncover the mechanisms of the pleiotropic effects of metformin
Description	Metformin is the most popular drug to treat type II diabetes. Besides lowering blood sugar, it is proven to have more beneficial effects, including extending life expectancy. However, the underlying mechanisms remain largely elusive. Here, we systematically studied the proteome thermal stability changes induced by a wide dosage range of metformin in a liver cancer cell line using the proteome integral solubility alteration (PISA) assay. This work provides valuable and unique information about the interactions between proteins and this drug, which is not able to obtain using commonly used abundance-based proteomics. The current results demonstrated that the most acceptable target of metformin responsible for lowering blood glucose levels, complex I, was stabilized only under the high-concentration metformin treatment. Intriguingly, the complex IV subunits were significantly stabilized by low concentrations of (such as 0.2 μM) metformin, indicating that the complex IV may play an important role in the sugar-lowering effect. Moreover, low-dose metformin significantly altered ribosome and histone protein stabilities, correlated with the inhibitive effect of cell proliferation by metformin. We further found that low-concentration metformin impacted mitochondrial cargo transport and vesicle transport, while high-concentration metformin affected cell redox responses and cell membrane protein sorting. Systematic investigation of metformin-induced proteome thermal stability changes provides intriguing insights into the molecular mechanisms of lowering blood sugar and the pleiotropic effects of metformin.
HostingRepository	PRIDE
AnnounceDate	2024-01-11
AnnouncementXML	Submission_2024-01-11_06:49:05.213.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kejun Yin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-13 05:31:35	ID requested
⏵ 1	2024-01-11 06:49:05	announced

10.1021/ACSPTSCI.3C00298;

submitter keyword: thermal proteome profiling,metformin, proteome integral solubility alteration assay

Ronghu Wu
contact affiliation	School of Chemistry and Biochemistry, Georgia Institute of Technology
contact email	ronghu.wu@chemistry.gatech.edu
lab head
Kejun Yin
contact affiliation	Georgia Institute of Technology
contact email	kyin49@gatech.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/01/PXD039382

PRIDE project URI

• PRIDE
  1. PXD039382
     1. Label: PRIDE project
     2. Name: Systematic investigation of dose-dependent protein thermal stability changes to uncover the mechanisms of the pleiotropic effects of metformin