PXD062018

PXD062018 is an original dataset announced via ProteomeXchange.

Title	Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia
Description	The maintenance of metabolic homeostasis relies on the ability to flexibly transit between catabolic and anabolic states in response to insulin signaling. Insulin-activated ATM is a critical mediator of this process, facilitating the swift transition between catabolic-and-anabolic fates of glucose by regulating the functional status of PKM2 and HIF1α. In Ataxia-Telangiectasia (A-T), these mechanisms are disrupted, resulting in intrinsic insulin resistance and glucose intolerance. Consequently, cells exhibit a compensatory dependence on glutamine as an alternative metabolite for energy metabolism. Cerebellar degeneration, a hallmark of A-T, is characterized by the pronounced vulnerability of Purkinje cells, attributed to their unexpected sensitivity to insulin. Supplementation with α-ketoglutarate, the α-keto acid backbone of glutamine, has demonstrated potentials in alleviating glutamine dependence and attenuating Purkinje cell degeneration. These findings suggest that peripheral metabolic deficiencies may contribute to sustained neurodegenerative changes in A-T, underscoring the importance of screening, monitoring and addressing these metabolic disruptions in patients.
HostingRepository	PRIDE
AnnounceDate	2025-10-23
AnnouncementXML	Submission_2025-10-23_05:24:33.033.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ka Li Jacquelyne Sun
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-19 01:02:08	ID requested
⏵ 1	2025-10-23 05:24:33	announced

10.1038/S41467-025-64360-8;

submitter keyword: Ataxia-Telangiectasia, Insulin Resistance, Metabolic Flexibility

Kim Hei-Man
contact affiliation	School of Life Sciences, The Chinese University of Hong Kong
contact email	heimanchow@cuhk.edu.hk
lab head
Ka Li Jacquelyne Sun
contact affiliation	The Chinese University of Hong Kong
contact email	kalijacquelynesun@cuhk.edu.hk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062018
     1. Label: PRIDE project
     2. Name: Alpha-ketoglutarate mitigates insulin resistance and metabolic inflexibility in a mouse model of Ataxia-Telangiectasia