ArticleMolecular cell2018
Dynamic Regulation of Long-Chain Fatty Acid Oxidation by a Noncanonical Interaction between the MCL-1 BH3 Helix and VLCAD.
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Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44citing papers in PubMed
5.8field-weighted citation impact, top 3% of its field
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients.Breast cancer research : BCR · 2019Trial
- MCL1 promotes porcine epidemic diarrhea virus replication by modulating arachidonic acid metabolic pathway.PLoS pathogens · 2026Article
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- HFrontiers in cell and developmental biology · 2026Review
- Pharmacological inhibition of MCL-1 disrupts mitochondrial cristae and depletes the human neural progenitor cell pool.bioRxiv : the preprint server for biology · 2025Article
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- MCL1 may not mediate chemoresistance.bioRxiv : the preprint server for biology · 2025Article
- Cell death and cancer: Metabolic interconnections.Cell reports · 2025Review
- A Pathway-Level Information ExtractoR (PLIER) framework to gain mechanistic insights into obesity in Down syndrome.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2025Article
- Dissecting the neuroprotective interaction between the BH4 domain of BCL-w and the IP3 receptor.Cell chemical biology · 2024Article
- Anti-apoptotic MCL-1 promotes long-chain fatty acid oxidation through interaction with ACSL1.Molecular cell · 2024Article
- Mitochondrial proteome research: the road ahead.Nature reviews. Molecular cell biology · 2024Review
- Hypomethylating agent decitabine sensitizes diffuse large B-cell lymphoma to venetoclax.Haematologica · 2024Article
- Targeting MCL-1 triggers DNA damage and an anti-proliferative response independent from apoptosis induction.Cell reports · 2023Article
- CPT1A-mediated fatty acid oxidation confers cancer cell resistance to immune-mediated cytolytic killing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulators mount up: the metabolic roles of apoptotic proteins.Frontiers in cell death · 2023Article
- Targeting metabolic vulnerabilities to overcome resistance to therapy in acute myeloid leukemia.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Targeting MCL-1 protein to treat cancer: opportunities and challenges.Frontiers in oncology · 2023Review
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Authors and funding
16 authors at 5 institutions in 1 country.
Silvia EscuderoDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Elma ZaganjorDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Susan LeeDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Christopher P MillDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Ann M MorganDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Emily B CrawfordDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jiahao ChenDepartments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Thomas E WalesDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Rida MourtadaDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
James LuccarelliDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Gregory H BirdDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Ulrich SteidlDepartments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
John R EngenDepartment of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Marcia C HaigisDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Joseph T OpfermanDepartment of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: joseph.opferman@stjude.org.
Loren D WalenskyDepartment of Pediatric Oncology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: loren_walensky@dfci.harvard.edu.
Dana-Farber Cancer Institute · USAlbert Einstein College of Medicine · USHarvard University · USNortheastern University · USSt. Jude Children's Research Hospital · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MViral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MSTRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4MMOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6MDissecting and Targeting Deregulated Mitochondrial Apoptosis in Human CancerR35CA197583 · NCI · DANA-FARBER CANCER INST · PI Loren David Walensky · 2015 to 2026
$12.5MStapled Peptides for Protein Interaction Research and Therapeutic Targeting in Human CancerR50CA211399 · NCI · DANA-FARBER CANCER INST · PI Gregory Howard Bird · 2016 to 2026
$3.2MRegulation of Cell Death and Mitochondrial Physiology by Anti-Apoptotic MCL-1R01HL102175 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI OPFERMAN, JOSEPH T. · 2010 to 2014
$2.1MPathway Specific Combinational Therapy in Poor Prognosis B-Lineage Acute Lymphoblastic LeukemiaR01CA201069 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI OPFERMAN, JOSEPH T. · 2016 to 2020
$2.0MMechanisms of Formation and Progression of Preleukemic Stem CellsR01CA217092 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STEIDL, ULRICH · 2017 to 2021
$2.0MRole of a Novel Homeobox Transcription Factor (HLX) in Acute Myeloid LeukemiaR01CA166429 · NCI · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STEIDL, ULRICH · 2013 to 2017
$1.9MRegulation of Cardiac Death and Energy Metabolism by MCL-1R01HL123543 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI OPFERMAN, JOSEPH T. · 2015 to 2018
$1.8MCIHR DFS-134963NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA166429NCI NIH HHS R01 CA201069NCI NIH HHS R01 CA217092NCI NIH HHS R35 CA197583NCI NIH HHS R50 CA211399NHLBI NIH HHS R01 HL102175NHLBI NIH HHS R01 HL123543NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK103295NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM008313
Abstract
MCL-1 is a BCL-2 family protein implicated in the development and chemoresistance of human cancer. Unlike its anti-apoptotic homologs, Mcl-1 deletion has profound physiologic consequences, indicative of a broader role in homeostasis. We report that the BCL-2 homology 3 (BH3) α helix of MCL-1 can directly engage very long-chain acyl-CoA dehydrogenase (VLCAD), a key enzyme of the mitochondrial fatty acid β-oxidation (FAO) pathway. Proteomic analysis confirmed that the mitochondrial matrix isoform of MCL-1 (MCL-1
Indexed as
Acyl-CoA Dehydrogenase, Long-ChainAnimalsCell LineLipid MetabolismMiceMice, KnockoutMyeloid Cell Leukemia Sequence 1 ProteinOxidation-ReductionPalmitic AcidProtein Structure, SecondaryAcyl-CoA Dehydrogenase, Long-ChainMcl1 protein, mouseMyeloid Cell Leukemia Sequence 1 ProteinPalmitic AcidapoptosisBCL-2 familyfatty acid metabolismMCL-1mitochondriamitochondrial matrixstapled peptideVLCADα helixβ-oxidation
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