A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue

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Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092
08:53

Biochemical and Structural Characterization of the Carbohydrate Transport Substrate-binding-protein SP0092

Published on: October 2, 2017

Vincenza Dolce1, Pasquale Scarcia, Domenico Iacopetta

  • 1Laboratory of Biochemistry and Molecular Biology, Department of Pharmaco-Biology, University of Bari, Via Orabona 4, 70125 Bari, Italy.

FEBS Letters
|January 27, 2005
PubMed

Insights

Researchers discovered AAC4, a new mitochondrial protein that transports ADP and ATP. This protein is found in liver, testis, and brain and functions similarly to other AACs.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Mitochondrial ADP/ATP carriers (AACs) are crucial for cellular energy metabolism by exchanging cytosolic ADP for matrix ATP.
  • The AAC subfamily comprises essential proteins involved in this vital transport process.

Purpose of the Study:

  • To identify and characterize a novel member of the AAC subfamily, designated AAC4.
  • To determine the localization, sequence identity, tissue distribution, and functional properties of AAC4.

Main Methods:

  • Gene mapping to identify the chromosomal location of AAC4.
  • Sequence analysis to compare AAC4 with known AAC proteins (AAC 1-3).
  • Mitochondrial localization studies.
  • Transcript analysis to determine tissue-specific expression.
  • Heterologous expression and liposome reconstitution to study transport mechanism and inhibitor sensitivity.

Main Results:

  • AAC4 is a novel mitochondrial metabolite transport protein, 66-68% identical to human AAC 1-3.
  • The AAC4 gene is located on human chromosome 4q28.1.
  • AAC4 transcripts are specifically detected in liver, testis, and brain.
  • AAC4 functions as an electrogenic ADP/ATP antiporter with high specificity.
  • AAC4 exhibits high sensitivity to carboxyatractyloside and bongkrekic acid.

Conclusions:

  • AAC4 represents a newly identified member of the mitochondrial ADP/ATP carrier family.
  • Its tissue-specific expression suggests specialized roles in energy metabolism within the liver, testis, and brain.
  • AAC4's transport mechanism and inhibitor sensitivity are consistent with its classification within the AAC subfamily.

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