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PXD046689-1

PXD046689 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMANF facilitates breast cancer cell survival under glucose starvation via PRKN-mediated mitophagy regulation
DescriptionGlucose 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.
HostingRepositoryiProX
AnnounceDate2023-11-06
AnnouncementXMLSubmission_2023-11-05_21:53:49.096.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZhenchong Xiong
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-05 21:52:29ID requested
12023-11-05 21:53:49announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Breast cancer, glucose starvation, ROS, mitophagy, MANF, PRKN
Contact List
Zhenchong Xiong
contact affiliationSun Yat-sen University Cancer Center
contact emailxiongzhch@sysucc.org.cn
lab head
Zhenchong Xiong
contact affiliationSun Yat-sen University Cancer Center
contact emailxiongzhch@sysucc.org.cn
dataset submitter
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