PXD031364

PXD031364 is an original dataset announced via ProteomeXchange.

Title	MCL-1 Drives a Metabolic Dependency on Fatty Acid Oxidation in Cancer Independent of its Anti-Apoptotic Function
Description	MCL-1 is an anti-apoptotic BCL-2 family protein essential to the survival of diverse cell types and is a major driver of cancer and chemoresistance. The unique oncogenic supremacy of MCL-1, as compared to its anti-apoptotic homologs, suggests that it has additional functions to complement apoptotic suppression. Here, we find that MCL-1-dependent hematologic cancer cells selectively rely on fatty acid oxidation (FAO) as a fuel source due to metabolic wiring enforced by MCL-1 itself. Importantly, this metabolic function is independent of anti-apoptotic activity, as demonstrated by metabolomic, proteomic, and genomic profiling of MCL-1-dependent leukemia cells lacking pro-apoptotic BAX and BAK. Genetic deletion of Mcl-1 results in selective downregulation of proteins within the FAO pathway, accompanied by cell death upon glucose deprivation despite apoptotic blockade. Our data reveal that MCL-1 drives a programmatic dependency on FAO in hematologic cancer cells, which can be effectively targeted by FAO inhibitors.
HostingRepository	PRIDE
AnnounceDate	2022-10-03
AnnouncementXML	Submission_2022-10-03_03:08:57.763.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-31 02:14:19	ID requested
⏵ 1	2022-10-03 03:08:58	announced

Dataset with its publication pending

submitter keyword: MCL-1, fatty acid oxidation, metabolism, cancer, apoptosis, BCL-2 family, mitochondria

Loren Walensky
contact affiliation	Department of Pediatric Oncology and Linde Program in Cancer Chemical Biology Dana-Farber Cancer Institute Boston, MA, USA
contact email	Loren_Walensky@dfci.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031364
     1. Label: PRIDE project
     2. Name: MCL-1 Drives a Metabolic Dependency on Fatty Acid Oxidation in Cancer Independent of its Anti-Apoptotic Function