OCIAD1 and prohibitins regulate the stability of the TIM23 protein translocase
Praveenraj Elancheliyan,
Klaudia K. Maruszczak,
Remigiusz Adam Serwa,
Till Stephan,
Ahmet Sadik Gulgec,
Mayra A. Borrero-Landazabal,
Sonia Ngati,
Aleksandra Gosk,
Stefan Jakobs,
Michal Wasilewski,
Agnieszka Chacinska
Affiliations
Praveenraj Elancheliyan
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; ReMedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Klaudia K. Maruszczak
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Remigiusz Adam Serwa
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Till Stephan
Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany; Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt am Main, Frankfurt am Main 60438, Germany
Ahmet Sadik Gulgec
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Mayra A. Borrero-Landazabal
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Sonia Ngati
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland
Aleksandra Gosk
Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland
Stefan Jakobs
Department of NanoBiophotonics, Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany; Department of Neurology, University Medical Center Göttingen, 37075 Göttingen, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Translational Neuroinflammation and Automated Microscopy TNM, 37075 Göttingen, Germany
Michal Wasilewski
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; Corresponding author
Agnieszka Chacinska
IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; ReMedy International Research Agenda Unit, IMol Polish Academy of Sciences, 02-247 Warsaw, Poland; Corresponding author
Summary: Mitochondrial proteins are transported and sorted to the matrix or inner mitochondrial membrane by the presequence translocase TIM23. In yeast, this essential and highly conserved machinery is composed of the core subunits Tim23 and Tim17. The architecture, assembly, and regulation of the human TIM23 complex are poorly characterized. The human genome encodes two paralogs, TIMM17A and TIMM17B. Here, we describe an unexpected role of the ovarian cancer immunoreactive antigen domain-containing protein 1 (OCIAD1) and the prohibitin complex in the biogenesis of human TIM23. Prohibitins were required to stabilize both the TIMM17A- and TIMM17B-containing variants of the translocase. Interestingly, OCIAD1 assembled with the prohibitin complex to protect the TIMM17A variant from degradation by the YME1L protease. The expression of OCIAD1 was in turn regulated by the status of the TIM23 complex. We postulate that OCIAD1 together with prohibitins constitute a regulatory axis that differentially regulates variants of human TIM23.
