Pleiotropic effects of the yeast Sal1 and Aac2 carriers on mitochondrial function via an activity distinct from adenine nucleotide transport

  • Blanka Kucejova
  • Li Li
  • Xiaowen Wang
  • Sergio Giannattasio
  • Xin Jie Chen
Original Paper

Abstract

In Saccharomyces cerevisiae, SAL1 encodes a Ca2+-binding mitochondrial carrier. Disruption of SAL1 is synthetically lethal with the loss of a specific function associated with the Aac2 isoform of the ATP/ADP translocase. This novel activity of Aac2 is defined as the V function (for Viability of aac2 sal1 double mutant), which is independent of the ATP/ADP exchange activity required for respiratory growth (the R function). We found that co-inactivation of SAL1 and AAC2 leads to defects in mitochondrial translation and mitochondrial DNA (mtDNA) maintenance. Additionally, sal1Δ exacerbates the respiratory deficiency and mtDNA instability of ggc1Δ, shy1Δ and mtg1Δ mutants, which are known to reduce mitochondrial protein synthesis or protein complex assembly. The V function is complemented by the human Short Ca2+-binding Mitochondrial Carrier (SCaMC) protein, SCaMC-2, a putative ATP-Mg/Pi exchangers on the inner membrane. However, mitochondria lacking both Sal1p and Aac2p are not depleted of adenine nucleotides. The Aac2R252I and Aac2R253I variants mutated at the R252-254 triplet critical for nucleotide transport retain the V function. Likewise, Sal1p remains functionally active when the R479I and R481I mutations were introduced into the structurally equivalent R479-T480-R481 motif. Finally, we found that the naturally occurring VR+ Aac1 isoform of adenine nucleotide translocase partially gains the V function at the expense of the R function by introducing the mutations P89L and A96 V. Thus, our data support the view that the V function is independent of adenine nucleotide transport associated with Sal1p and Aac2p and this evolutionarily conserved activity affects multiple processes in mitochondria.

Keywords

Mitochondria Adenine nucleotide translocase Sal1 Ca2+-binding Transport 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Blanka Kucejova
    • 1
  • Li Li
    • 1
    • 2
  • Xiaowen Wang
    • 1
    • 2
  • Sergio Giannattasio
    • 3
  • Xin Jie Chen
    • 1
    • 2
  1. 1.Department of Molecular BiologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Biochemistry and Molecular BiologySUNY Upstate Medical UniversitySyracuseUSA
  3. 3.CNR, Istituto di Biomembrane e BioenergeticaBariItaly

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