Hwang David K, Claypool Steven M, Leuenberger Danielle, Tienson Heather L, Koehler Carla M
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
J Cell Biol. 2007 Sep 24;178(7):1161-75. doi: 10.1083/jcb.200706195.
Tim54p, a component of the inner membrane TIM22 complex, does not directly mediate the import of inner membrane substrates but is required for assembly/stability of the 300-kD TIM22 complex. In addition, Deltatim54 yeast exhibit a petite-negative phenotype (also observed in yeast harboring mutations in the F1Fo ATPase, the ADP/ATP carrier, mitochondrial morphology components, or the i-AAA protease, Yme1p). Interestingly, other import mutants in our strain background are not petite-negative. We report that Tim54p is not involved in maintenance of mitochondrial DNA or mitochondrial morphology. Rather, Tim54p mediates assembly of an active Yme1p complex, after Yme1p is imported via the TIM23 pathway. Defective Yme1p assembly is likely the major contributing factor for the petite-negativity in strains lacking functional Tim54p. Thus, Tim54p has two independent functions: scaffolding/stability for the TIM22 membrane complex and assembly of Yme1p into a proteolytically active complex. As such, Tim54p links protein import, assembly, and turnover pathways in the mitochondrion.
Tim54p是内膜TIM22复合物的一个组成部分，它并不直接介导内膜底物的导入，但对于300-kD TIM22复合物的组装/稳定性是必需的。此外，缺失Tim54p的酵母表现出小菌落阴性表型（在F1Fo ATP酶、ADP/ATP载体、线粒体形态成分或i-AAA蛋白酶Yme1p发生突变的酵母中也观察到这种表型）。有趣的是，我们菌株背景中的其他导入突变体并非小菌落阴性。我们报告称，Tim54p不参与线粒体DNA的维持或线粒体形态的维持。相反，在Yme1p通过TIM23途径导入后，Tim54p介导活性Yme1p复合物的组装。Yme1p组装缺陷可能是缺乏功能性Tim54p的菌株中出现小菌落阴性的主要因素。因此，Tim54p具有两个独立的功能：为TIM22膜复合物提供支架/稳定性以及将Yme1p组装成具有蛋白水解活性的复合物。据此，Tim54p将线粒体中的蛋白质导入、组装和周转途径联系起来。
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