Evidence map›Paper›PMID 39763924›Full record

ArticlebioRxiv : the preprint server for biology2024

A gated hydrophobic funnel within BAX binds long-chain alkenals to potentiate pro-apoptotic function.

Jesse D Gelles, Yiyang Chen, Mark P A Luna-Vargas, Ariele Viacava Follis, Stella G Bayiokos, Jarvier N Mohammed, Tara M Sebastian, M Abdullah Al Noman, Ngoc Dung Pham, Yi Shi and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jesse D GellesLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.ORCID 0000-0002-3960-1853
Yiyang ChenLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Mark P A Luna-VargasLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Ariele Viacava FollisDepartment of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Stella G BayiokosLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Jarvier N MohammedLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Tara M SebastianLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
M Abdullah Al NomanLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Ngoc Dung PhamDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Yi ShiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.
Richard W KriwackiDepartment of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
Jerry E ChipukLaboratory of Mitochondrial Biology in Human Health and Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, New York 10029, USA.ORCID 0000-0002-1337-842X

Funding

THE TISCH CANCER INSTITUTE - CANCER CENTER SUPPORT GRANTP30CA196521 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ramon E Parsons · 2015 to 2026
$35.4M
Chronic Mitochondrial Division and Melanoma: Mechanism, Prognosis, and TherapyR01CA267696 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Jerry Edward Chipuk · 2022 to 2026
$2.4M
The Oncogene Activated Mitochondrial Unfolded Protein Response Regulates Senescence BiologyR01CA271346 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Jerry Edward Chipuk · 2023 to 2026
$2.4M
Function and Regulation of the BCL-2 FamilyR01CA237264 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2020 to 2024
$1.9M
Function and regulation of the BCL-2 familyR01CA157740 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2011 to 2015
$1.7M
Understanding the Structural Mechanism of Puma-induced ApoptosisR01GM083159 · NIGMS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI KRIWACKI, RICHARD W · 2009 to 2012
$1.3M
Ethanol-mediated inhibition of the S1P lyase results in disruption of apoptotic machinery and lymphocyte egress from lymphoid tissueF31AA024681 · NIAAA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELLES-HURWITZ, JESSE · 2015 to 2018
$155k
NCI NIH HHS P30 CA196521NCI NIH HHS R01 CA157740NCI NIH HHS R01 CA237264NCI NIH HHS R01 CA267696NCI NIH HHS R01 CA271346NIAAA NIH HHS F31 AA024681NIGMS NIH HHS R01 GM083159
6 · The paper itself

Abstract

Mitochondria maintain a biochemical environment that cooperates with BH3-only proteins (e.g., BIM) to potentiate BAX activation, the key event to initiate physiological and pharmacological forms of apoptosis. The sphingosine-1-phosphate metabolite 2-trans-hexadecenal (2t-hexadecenal) is one such component described to support BAX activation, but molecular mechanisms remain largely unknown. Here, we utilize complementary biochemical and biophysical techniques to reveal that 2t-hexadecenal non-covalently interacts with BAX, and cooperates with BIM to stimulate early-activation steps of monomeric BAX. Integrated structural and computational approaches reveal 2t-hexadecenal binds an undefined region - a hydrophobic cavity formed by core-facing residues of α5, α6, and gated by α8 - we now term the "BAX actuating funnel" (BAF). We define alkenal length and α8 mobility as critical determinants for 2t-hexadecenal synergy with BIM and BAX, and demonstrate that proline 168 allosterically regulates BAF function. Collectively, this work imparts detailed molecular insights advancing our fundamental knowledge of BAX regulation and identifies a regulatory region with implications for biological and therapeutic opportunities.

Indexed as

ApoptosisBAXBCL-2 FamilyCell DeathHexadecenalMOMPα,β-Unsaturated Alkenals

Identifiers

PMID39763924
PMCPMC11703243

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.