PXD046689

PXD046689 is an original dataset announced via ProteomeXchange.

Title	MANF facilitates breast cancer cell survival under glucose starvation via PRKN-mediated mitophagy regulation
Description	Glucose shortage can lead to ROS accumulation and thus induce mitochondrial damage in breast cancer (BC) cells. However, the role of mitophagy in cancer cells under glucose starvation remains unclear. Here, we showed that mesencephalic astrocyte-derived neurotrophic factor (MANF)-mediated mitophagy facilitates BC cell survival under glucose starvation. MANF-mediated mitophagy also promotes fatty acid oxidation in glucose-starved BC cells. Moreover, under glucose starvation, SENP1-mediated de-SUMOylation of MANF increases cytoplasmic MANF expression through the inhibition of MANF’s nuclear translocation and hence renders mitochondrial distribution of MANF. MANF mediates mitophagy by binding to parkin RBR E3 ubiquitin protein ligase (PRKN), a key mitophagy regulator, in the mitochondria. Under glucose starvation, protein oxidation inhibits PRKN activity; nevertheless, CXXC motif of MANF alleviates protein oxidation in RING II-domain of PRKN and restores its E3 ligase activity. Furthermore, MANF–PRKN interactions are essential for BC tumor growth and metastasis. High MANF expression predicts poor outcomes in patients with BC. Our results provide a mechanistic explanation for the prosurvival role of MANF-mediated mitophagy in BC cells under glucose starvation and may point to targetable vulnerabilities.
HostingRepository	iProX
AnnounceDate	2023-11-06
AnnouncementXML	Submission_2023-11-05_21:53:49.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhenchong Xiong
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-05 21:52:29	ID requested
⏵ 1	2023-11-05 21:53:49	announced

Dataset with its publication pending

submitter keyword: Breast cancer, glucose starvation, ROS, mitophagy, MANF, PRKN

Zhenchong Xiong
contact affiliation	Sun Yat-sen University Cancer Center
contact email	xiongzhch@sysucc.org.cn
lab head
Zhenchong Xiong
contact affiliation	Sun Yat-sen University Cancer Center
contact email	xiongzhch@sysucc.org.cn
dataset submitter

iProX dataset URI