Role of mitochondrial Hsp70 (mtHsp70) in the assembly of the F1FO-ATP synthase
Jiyao Song1, Liesa Steidle, Lena Böttinger, Nikolaus Pfanner1 andThomas Becker1 1Institute for Biochemistry and Molecular Biology, Faculty of Medicine, University of Freiburg
Mitochondria, the power plants of the eukaryotic cells, are essential for adenosine triphosphate (ATP) generation and also for a variety of metabolic reactions. The mitochondrial F1FO-ATP synthase (ATP synthase) utilizes the proton gradient generated by the respiratory chain to produce ATP for cellular metabolism. Partial deficiency of the ATP synthase causes severe inherited mitochondria diseases. Yeast mitochondrial ATP synthase consists of 17 subunits that are arranged in three main modules: the FO part that sits in the mitochondrial inner membrane, the matrix residing F1 part, and the peripheral stalk that links the FO and F1 regions. The components of the ATP synthase are of dual origin. The mitochondrial DNA encodes for three subunits, while the rest subunits are nuclear encoded. The latter proteins are synthesized on cytosolic ribosomes and then imported into mitochondria via the translocase of the outer mitochondrial membrane (TOM complex) and the presequence translocase (TIM23 complex). The import of matrix-localized subunits of the ATP synthase additionally depends on the activity of mtHsp70, which is the core subunit of the presequence translocase-associated motor (PAM). How the different originated subunits assemble into a functional protein machinery is only understood in part. Previously, Atp11 and Atp12 have been described as assembly factors for the F1 part of the ATP synthase. In addition, a role of the INA complex in later assembly steps has been reported. However, it remains unknown how the imported subunits are delivered from the TIM23 complex into the assembly line of the ATP synthase. Here, we identified a novel role of the mtHsp70 in the assembly of the ATP synthase. Using specific mutant allele of SSC1 encoding for mtHsp70, we could separate the role of mtHsp70 in protein import from its function in the formation of the ATP synthase. Thus, our results point to a novel link of protein import via TIM23 complex and PAM with the assembly of the ATP synthase.
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