Investigation of TOMM20 Interactome in Relation to Protein Quality Control and Translocation

by Metin Özdemir
Doctoral thesis
Date of Examination:2023-11-09
Date of issue:2024-11-11
Advisor:Prof. Dr. Peter Rehling
Referee:Prof. Dr. Henning Urlaub
Referee:Dr. Alexander Stein
Persistent Address: http://dx.doi.org/10.53846/goediss-10850

 

 

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Abstract

English

The human mitochondria are home to a vast repertoire of approximately 1,500 proteins, most of which are synthesized within the cytosol and post-translationally translocated into the mitochondria. Amidst the intricate machinery of mitochondrial translocases, the Translocase of the Outer Membrane (TOM) complex takes center stage, facilitating most of the translocation events, if not the entirety. Thus, understanding the inner workings of this complex is of considerable scientific importance. While the structures of the TOM complex for yeast and humans have been available for some time, the nuanced regulation of the translocation process remains an enduring enigma in humans. In light of this, deciphering the interactome of the TOM complex emerges as a crucial endeavor. Although prior investigations in yeast models have elucidated interactions between the TOM complex and various entities such as the Sorting and Assembly Machinery (SAM) complex, Mitochondrial Contact Site, and Cristae Organizing System (MICOS) complex, as well as Voltage-Dependent Anion Channels (VDACs), the direct establishment of these interactions within the context of human mitochondria has remained absent. Hence, our study seeks to address this gap by systematically exploring the proteome associated with the TOM complex, employing TOMM20 as the molecular bait. Our experiments successfully unveiled interactions between the TOM complex and the SAM complex, MICOS complex, and VDACs, thereby shedding new light on the intricate network of mitochondrial protein translocation and interactions within the human system. We have also identified unexpected players such as MUL1, ATAD1, MTCH1, MTCH2, MARC2, and TRABD among the interacting proteins. We have investigated their roles in the quality control of mitochondrial protein translocation and their involvement in its regulation and modulation. Notably, our findings indicate that the absence of TRABD appears to exert a discernible impact on the carrier pathway import, which warrants further in-depth research.
Keywords: mitochondria; tom complex; quality control
 
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