CLiB - a novel cardiolipin-binder isolated via data-driven and in vitro screening

Publication type:
Journal article
Metadata:
Abstract
<jats:p>CLiB, a cardiolipin-binding molecules, affects respiration of cardiolipin-containing bacteria as well as of mitochondria.</jats:p>
Autoren
  • Isabel Kleinwächter
  • Bernadette Mohr
  • Aljoscha Joppe
  • Nadja Hellmann
  • Tristan Bereau
  • Heinz D Osiewacz
  • Dirk Schneider
DOI
10.1039/d2cb00125j
eISSN
2633-0679
Ausgabe der Veröffentlichung
7
Zeitschrift
RSC Chemical Biology
Sprache
en
Online publication date
2022
Paginierung
941 - 954
Status
Published online
Herausgeber
Royal Society of Chemistry (RSC)
Herausgeber URL
http://dx.doi.org/10.1039/d2cb00125j
Datum der Datenerfassung
2024
Titel
CLiB – a novel cardiolipin-binder isolated <i>via</i> data-driven and <i>in vitro</i> screening
Ausgabe der Zeitschrift
3

Data source: Crossref

Other metadata sources:
Abstract
Cardiolipin, the mitochondria marker lipid, is crucially involved in stabilizing the inner mitochondrial membrane and is vital for the activity of mitochondrial proteins and protein complexes. Directly targeting cardiolipin by a chemical-biology approach and thereby altering the cellular concentration of "available" cardiolipin eventually allows to systematically study the dependence of cellular processes on cardiolipin availability. In the present study, physics-based coarse-grained free energy calculations allowed us to identify the physical and chemical properties indicative of cardiolipin selectivity and to apply these to screen a compound database for putative cardiolipin-binders. The membrane binding properties of the 22 most promising molecules identified in the <i>in silico</i> approach were screened <i>in vitro</i>, using model membrane systems finally resulting in the identification of a single molecule, CLiB (CardioLipin-Binder). CLiB clearly affects respiration of cardiolipin-containing intact bacterial cells as well as of isolated mitochondria. Thus, the structure and function of mitochondrial membranes and membrane proteins might be (indirectly) targeted and controlled by CLiB for basic research and, potentially, also for therapeutic purposes.
Addresses
  • Department of Chemistry, Biochemistry, Johannes Gutenberg University Mainz Hanns-Dieter-Hüsch-Weg 17 55128 Mainz Germany Dirk.Schneider@uni-mainz.de.
Autoren
  • Isabel Kleinwächter
  • Bernadette Mohr
  • Aljoscha Joppe
  • Nadja Hellmann
  • Tristan Bereau
  • Heinz D Osiewacz
  • Dirk Schneider
DOI
10.1039/d2cb00125j
eISSN
2633-0679
Externe Identifier
  • PubMed Identifier: 35866160
  • PubMed Central ID: PMC9257654
Open access
true
ISSN
2633-0679
Ausgabe der Veröffentlichung
7
Zeitschrift
RSC chemical biology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2022
Open access status
Open Access
Paginierung
941 - 954
Datum der Veröffentlichung
2022
Status
Published
Publisher licence
CC BY-NC
Datum der Datenerfassung
2022
Titel
CLiB - a novel cardiolipin-binder isolated <i>via</i> data-driven and <i>in vitro</i> screening.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
3

Files

https://pubs.rsc.org/en/content/articlepdf/2022/cb/d2cb00125j https://europepmc.org/articles/PMC9257654?pdf=render

Data source: Europe PubMed Central

Abstract
Cardiolipin, the mitochondria marker lipid, is crucially involved in stabilizing the inner mitochondrial membrane and is vital for the activity of mitochondrial proteins and protein complexes. Directly targeting cardiolipin by a chemical-biology approach and thereby altering the cellular concentration of "available" cardiolipin eventually allows to systematically study the dependence of cellular processes on cardiolipin availability. In the present study, physics-based coarse-grained free energy calculations allowed us to identify the physical and chemical properties indicative of cardiolipin selectivity and to apply these to screen a compound database for putative cardiolipin-binders. The membrane binding properties of the 22 most promising molecules identified in the in silico approach were screened in vitro, using model membrane systems finally resulting in the identification of a single molecule, CLiB (CardioLipin-Binder). CLiB clearly affects respiration of cardiolipin-containing intact bacterial cells as well as of isolated mitochondria. Thus, the structure and function of mitochondrial membranes and membrane proteins might be (indirectly) targeted and controlled by CLiB for basic research and, potentially, also for therapeutic purposes.
Date of acceptance
2022
Autoren
  • Isabel Kleinwächter
  • Bernadette Mohr
  • Aljoscha Joppe
  • Nadja Hellmann
  • Tristan Bereau
  • Heinz D Osiewacz
  • Dirk Schneider
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/35866160
DOI
10.1039/d2cb00125j
eISSN
2633-0679
Externe Identifier
  • PubMed Central ID: PMC9257654
Ausgabe der Veröffentlichung
7
Zeitschrift
RSC Chem Biol
Sprache
eng
Country
England
Paginierung
941 - 954
PII
d2cb00125j
Datum der Veröffentlichung
2022
Status
Published online
Titel
CLiB - a novel cardiolipin-binder isolated via data-driven and in vitro screening.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
3

Data source: PubMed

Abstract
<jats:p>CLiB, a cardiolipin-binding molecules, affects respiration of cardiolipin-containing bacteria as well as of mitochondria.</jats:p>
Autoren
  • Isabel Kleinwächter
  • Bernadette Mohr
  • Aljoscha Joppe
  • Nadja Hellmann
  • Tristan Bereau
  • Heinz D Osiewacz
  • Dirk Schneider
DOI
10.1039/d2cb00125j
eISSN
2633-0679
Ausgabe der Veröffentlichung
7
Zeitschrift
RSC Chemical Biology
Sprache
en
Online publication date
2022
Paginierung
941 - 954
Status
Published online
Herausgeber
Royal Society of Chemistry (RSC)
Herausgeber URL
http://dx.doi.org/10.1039/d2cb00125j
Datum der Datenerfassung
2022
Titel
CLiB - a novel cardiolipin-binder isolated via data-driven and in vitro screening
Ausgabe der Zeitschrift
3

Data source: Manual

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