PXD056351-1

PXD056351 is an original dataset announced via ProteomeXchange.

Title	AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress
Description	Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here, we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B (ALDOB) accounts for glycerol biosynthesis by forming a complex with glycerol-3-phosphate dehydrogenases, GPD1 and GPD1L. Blocking GPD1, GPD1L, or glycerol 3-phosphate phosphatase exacerbates reductive stress and suppresses cell proliferation under hypoxia and tumor growth in vivo. Over-expression of these enzymes increases glycerol excretion but still reduces cell viability under hypoxia and tumor proliferation due to energy stress. AMPK inactivates ALDOB to mitigate glycerol synthesis that dissipates ATP, alleviating NADH accumulation-induced energy crisis. Therefore, glycerol biosynthesis/excretion regulates the trade-off between reductive stress and energy stress. Moreover, this mode of regulation seems to be prevalent in reductive stress-driven transformations, enhancing our understanding of the metabolic complexity and guiding tumor treatment.
HostingRepository	iProX
AnnounceDate	2024-09-29
AnnouncementXML	Submission_2024-09-28_20:49:56.023.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ronghui Yang
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-28 20:42:01	ID requested
⏵ 1	2024-09-28 20:49:56	announced

Dataset with its publication pending

submitter keyword: Phosphorylation sites, ALDOB, PGP

Binghui Li
contact affiliation	Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University
contact email	bli@ccmu.edu.cn
lab head
Ronghui Yang
contact affiliation	Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University
contact email	rhy_yangronghui@sina.com
dataset submitter

iProX dataset URI