Title (eng)
Exploring the proton transport mechanism of the mitochondrial ADP/ATP carrier: FA-cycling hypothesis and beyond
Mario Vazdar
Abstract (eng)
The mitochondrial ADP/ATP carrier (AAC, ANT), a member of the SLC25 family of solute carriers, plays a critical role in transporting purine nucleotides (ATP and ADP) as well as protons across the inner mitochondrial membrane. However, the precise mechanism and physiological significance of proton transport by ADP/ATP carrier remain unclear. Notably, the presence of uncouplers-such as long-chain fatty acids (FA) or artificial compounds like dinitrophenol (DNP)-is essential for this process. We explore two potential mechanisms that describe ADP/ATP carrier as either (i) a proton carrier that functions in the presence of FA or DNP, or (ii) an anion transporter (FA- or DNP). In the latter case, the proton is translocated by the neutral form of FA, which carries it from the matrix to the intermembrane space (FA-cycling hypothesis). Our recent results support this hypothesis. We describe a four-step mechanism for the "sliding" of the FA anion from the matrix to the mitochondrial intermembrane space and discuss a possible generalization of this mechanism to other SLC25 carriers.
Keywords (eng)
Mitochondrial ADP, ATP Translocases MetabolismMitochondrial ADP, ATP Translocases ChemistryProtonsFatty Acids MetabolismHumansAnimalsMitochondria MetabolismIon TransportMitochondrial Membranes Metabolism2,4-Dinitrophenol Pharmacology2,4-Dinitrophenol Metabolism
Type (eng)
Language
[eng]
Persistent identifier
Is in series
Title (eng)
Protein Science
Volume
34
Issue
3
ISSN
1469-896X
Issued
2025
Number of pages
14
Publication
Wiley
Version type (eng)
Date issued
2025
Access rights (eng)
License
Rights statement (eng)
© 2025 The Author(s)
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