Claypool Steven M, Oktay Yavuz, Boontheung Pinmanee, Loo Joseph A, Koehler Carla M
Department of Chemistry and Biochemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
J Cell Biol. 2008 Sep 8;182(5):937-50. doi: 10.1083/jcb.200801152.
Defined mutations in the mitochondrial ADP/ATP carrier (AAC) are associated with certain types of progressive external ophthalmoplegia. AAC is required for oxidative phosphorylation (OXPHOS), and dysregulation of AAC has been implicated in apoptosis. Little is known about the AAC interactome, aside from a known requirement for the phospholipid cardiolipin (CL) and that it is thought to function as a homodimer. Using a newly developed dual affinity tag, we demonstrate that yeast AAC2 physically participates in several protein complexes of distinct size and composition. The respiratory supercomplex and several smaller AAC2-containing complexes, including other members of the mitochondrial carrier family, are identified here. In the absence of CL, most of the defined interactions are destabilized or undetectable. The absence of CL and/or AAC2 results in distinct yet additive alterations in respiratory supercomplex structure and respiratory function. Thus, a single lipid can significantly alter the functional interactome of an individual protein.
线粒体ADP/ATP载体（AAC）中的特定突变与某些类型的进行性眼外肌麻痹相关。氧化磷酸化（OXPHOS）需要AAC，并且AAC的失调与细胞凋亡有关。除了对磷脂心磷脂（CL）的已知需求以及认为它作为同型二聚体发挥作用外，关于AAC相互作用组知之甚少。使用新开发的双亲和标签，我们证明酵母AAC2实际参与了几种大小和组成不同的蛋白质复合物。这里鉴定出了呼吸超复合物和几个较小的含AAC2的复合物，包括线粒体载体家族的其他成员。在没有CL的情况下，大多数已确定的相互作用不稳定或无法检测到。CL和/或AAC2的缺失导致呼吸超复合物结构和呼吸功能出现明显但累加的改变。因此，单一脂质可显著改变单个蛋白质的功能相互作用组。
