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The role of cardiolipin in defining the mammalian ANT interactome
Author(s) -
Lu YaWen,
Baile Matthew Garrett,
Huang TaiChung,
Pandey Akhilesh,
Claypool Steven Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1026.3
Subject(s) - interactome , ant , stable isotope labeling by amino acids in cell culture , saccharomyces cerevisiae , biology , immunoprecipitation , microbiology and biotechnology , cardiolipin , biochemistry , yeast , context (archaeology) , computational biology , proteomics , gene , membrane , ecology , phospholipid , paleontology
The major ADP/ATP carrier (AAC in yeast; ANT in mammals) in Saccharomyces cerevisiae , AAC2, mediates the 1:1 exchange of ADP into and ATP out of the mitochondrial matrix and is thus a required component of the oxidative phosphorylation machinery. Originally modeled to function in isolation, we recently demonstrated that yAAC2 associates with non‐yAAC2 partner proteins, including the respiratory supercomplex, in the context of cardiolipin (CL)‐containing membranes. As very little is known about the mammalian ANT interactome, this project aims to define the mammalian ANT interactome and determine if these interactions, like yAAC2, exhibit CL‐dependency. Using a combination of structural and mutational analyses, blue native‐PAGE, co‐immunoprecipitation, and stable isotope labeling by amino acids in cell culture (SILAC) on yeast, cell culture, and primary tissue models, we will determine the players that interact with mammalian ANT and the role CL plays in mediating these interactions. Results generated will allow for a more comprehensive understanding of the importance of the mammalian ANT interactome in health and disease. This work is supported by NHLBI grant R00HL089185 (SMC) and American Heart Association Predoctoral Fellowships 12PRE11910004 (YL) and 10PRE3280013 (MGB).