Evidence map›Paper›PMID 37205478›Full record

ArticlebioRxiv : the preprint server for biology2023

Conserved cardiolipin-mitochondrial ADP/ATP carrier interactions assume distinct structural and functional roles that are clinically relevant.

Nanami Senoo, Dinesh K Chinthapalli, Matthew G Baile, Vinaya K Golla, Bodhisattwa Saha, Oluwaseun B Ogunbona, James A Saba, Teona Munteanu, Yllka Valdez, Kevin Whited and 5 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 2 countries.

Nanami SenooDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dinesh K ChinthapalliPhysical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
Matthew G BaileDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Vinaya K GollaDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Bodhisattwa SahaPhysical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
Oluwaseun B OgunbonaDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
James A SabaDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Teona MunteanuDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yllka ValdezDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kevin WhitedDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dror ChorevPhysical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
Nathan N AlderDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Eric R MayDepartment of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Carol V RobinsonPhysical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QU, UK.
Steven M ClaypoolDepartment of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Johns Hopkins University · USUniversity of Oxford · GBUniversity of Connecticut · US

Funding

BIOCHEMISTRY, CELLULAR AND MOLECULAR BIOLOGY PROGRAMT32GM007445 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI GREEN, RACHEL · 1985 to 2021
$24.1M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Structural Dynamics of Viral Proteins: Development and Application of Multiscale Computational Methods for Studying Viral Capsids, Proteins and Membrane SystemsR35GM119762 · NIGMS · UNIVERSITY OF CONNECTICUT STORRS · PI Eric Robert May · 2016 to 2026
$4.1M
An intimate and multifaceted partnership: cardiolipin and the mitochondrial ADP/ATP carrierR01HL165729 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Steven Michael Claypool · 2023 to 2026
$2.1M
Cardiolipin and the mitochondrial ADP/ATP carrier interactomeR01HL108882 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI CLAYPOOL, STEVEN MICHAEL · 2013 to 2017
$2.0M
Defining protein synthesis demands and specificities in multiple myelomaF30CA260910 · NCI · JOHNS HOPKINS UNIVERSITY · PI SABA, JAMES ANDREW · 2021 to 2023
$155k
NCI NIH HHS F30 CA260910NHLBI NIH HHS R01 HL108882NHLBI NIH HHS R01 HL165729NIGMS NIH HHS R35 GM119762NIGMS NIH HHS T32 GM007445NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

The mitochondrial phospholipid cardiolipin (CL) promotes bioenergetics via oxidative phosphorylation (OXPHOS). Three tightly bound CLs are evolutionarily conserved in the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) which resides in the inner mitochondrial membrane and exchanges ADP and ATP to enable OXPHOS. Here, we investigated the role of these buried CLs in the carrier using yeast Aac2 as a model. We introduced negatively charged mutations into each CL-binding site of Aac2 to disrupt the CL interactions via electrostatic repulsion. While all mutations disturbing the CL-protein interaction destabilized Aac2 monomeric structure, transport activity was impaired in a pocket-specific manner. Finally, we determined that a disease-associated missense mutation in one CL-binding site in ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions.

Identifiers

PMID37205478
PMCPMC10187269
OpenAlexW4375868030

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.