PXD063885

PXD063885 is an original dataset announced via ProteomeXchange.

Title	PGC1-α drives Mfn2-linked Mitochondrial Fusion aiding Glioblastoma Cell Survival under TMZ stress
Description	Glioblastoma Multiforme (GBM) is an extremely aggressive primary brain-tumor with a median-survival rate of < 2 years. Higher risk in surgery has shifted the treatment paradigm towards combined chemotherapies. Interestingly, arduous dependency on chemotherapy has shown recurrence. Recent studies have portrayed the role of mitochondrial dynamics for survival under drug-pressure leading to recurrence. However, such studies exploring the role of mitochondria in response to drug stress in GBM are limited. Here we show that PGC1α (Peroxisome Proliferator-activated Receptor Gamma coactivator-1 Alpha) upregulates Mfn2 (Mitofusin 2) enhancing mitochondrial-fusion in GBM cells contributing to survival under profound Temozolomide (TMZ) stress. The interaction of PGC1α with SET1 compass / compass-like complex induces H3K4me3 trimethylations at the promoter regions of Mfn2 leading to an open chromatin assisting Mfn2 upregulation. The latter is further involved in inducing mitochondrial fusion, promoting oxidative phosphorylation which supports cell survival under stress. Notably, this further corroborates with our observations in the patient samples and clinical data where upregulation of Mfn2 was concurrently observed with elevated levels of PGC1α simultaneously leading to poor prognosis. Thus, this study provides critical insights into the molecular regulation of mitochondrial dynamics-dependent survival mechanisms in GBM that could further be exploited to design future therapies.
HostingRepository	PRIDE
AnnounceDate	2025-10-10
AnnouncementXML	Submission_2025-10-10_01:13:40.385.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sudeshna Mukherjee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-13 05:45:59	ID requested
⏵ 1	2025-10-10 01:13:40	announced

Dataset with its publication pending

submitter keyword: Mitochondrial fusion,Glioblastoma, Mfn2, Temozolomide, PGC1α

Prof. Sudeshna Mukherjee
contact affiliation	Cancer Biology Lab, Dept. of Biological Sciences, BITS Pilani
contact email	sudeshna@pilani.bits-pilani.ac.in
lab head
Sudeshna Mukherjee
contact affiliation	Cancer Biology Lab, Dept. of Biological Sciences, BITS Pilani
contact email	sudeshna@pilani.bits-pilani.ac.in
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063885
     1. Label: PRIDE project
     2. Name: PGC1-α drives Mfn2-linked Mitochondrial Fusion aiding Glioblastoma Cell Survival under TMZ stress