Human mitochondrial ADP/ATP carrier SLC25A4 operates with a ping-pong kinetic mechanism.
ADP/ATP translocase
SLC25
adenine nucleotide translocator
bioenergetics
mitochondrial carrier family
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
03 08 2023
03 08 2023
Historique:
revised:
17
05
2023
received:
06
03
2023
accepted:
17
05
2023
medline:
4
8
2023
pubmed:
6
6
2023
entrez:
6
6
2023
Statut:
ppublish
Résumé
The mitochondrial ADP/ATP carrier (SLC25A4), also called the adenine nucleotide translocase, imports ADP into the mitochondrial matrix and exports ATP, which are key steps in oxidative phosphorylation. Historically, the carrier was thought to form a homodimer and to operate by a sequential kinetic mechanism, which involves the formation of a ternary complex with the two exchanged substrates bound simultaneously. However, recent structural and functional data have demonstrated that the mitochondrial ADP/ATP carrier works as a monomer and has a single substrate binding site, which cannot be reconciled with a sequential kinetic mechanism. Here, we study the kinetic properties of the human mitochondrial ADP/ATP carrier by using proteoliposomes and transport robotics. We show that the Km/Vmax ratio is constant for all of the measured internal concentrations. Thus, in contrast to earlier claims, we conclude that the carrier operates with a ping-pong kinetic mechanism in which substrate exchange across the membrane occurs consecutively rather than simultaneously. These data unite the kinetic and structural models, showing that the carrier operates with an alternating access mechanism.
Identifiants
pubmed: 37278158
doi: 10.15252/embr.202357127
pmc: PMC10398649
doi:
Substances chimiques
Mitochondrial ADP, ATP Translocases
9068-80-8
Adenosine Triphosphate
8L70Q75FXE
Adenosine Diphosphate
61D2G4IYVH
SLC25A4 protein, human
0
Adenine Nucleotide Translocator 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e57127Subventions
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00028/2
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
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