ABSTRACT
The mitochondrial proteome arises from dual genetic origins. Nuclear-encoded proteins need to be transported across or inserted into two distinguished membranes, and the translocase of the outer mitochondrial membrane (TOM) complex represents the main translocase in the outer mitochondrial membrane. Its composition and regulation have been extensively investigated within yeast cells. However, we have little knowledge of the TOM complex composition within human cells. Here, we have defined the TOM interactome in a comprehensive manner using biochemical approaches to isolate the TOM complex in combination with quantitative mass spectrometry analyses. With these studies, we defined the pleiotropic nature of the human TOM complex, including new interactors, such as TRABD. Our studies provide a framework to understand the various biogenesis pathways that merge at the TOM complex within human cells.
Footnotes
Author contributions
Conceptualization: S.D., M.Ö., M.M., A.V., R.Y., B.W.; Data curation: S.D., M.Ö., S.O., A.S., M.M., A.V., R.Y., B.W.; Formal analysis: S.O., A.S., M.M., B.W.; Investigation: M.Ö.; Methodology: S.D., M.Ö., S.O., A.S., M.M., R.Y., B.W.; Project administration: S.D., B.W.; Supervision: S.D., B.W.; Validation: S.D., M.Ö., S.O., A.V.; Visualization: R.Y.; Writing – original draft: S.D.; Writing – review & editing: S.D., M.Ö., S.O., A.V., B.W.
Funding
This research project was funded by the Ministry for Science and Culture of Lower Saxony and Volkswagen Foundation no. 762-12-9/19 (ZN3457) (to S.D.), and the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) Sonderforschungsbereich (SFB)1286 (project number A06-1334776 to Prof. Peter Rehling), SFB1381, project number 403222702 (project B05 to B.W.) and SPP2453, project number 541758684 (to B.W. and S.D.), and supported by the International Max Planck Research School for Genome Science (M.Ö.), and by the PhD program Molecular Biology-International Max Planck Research School and the Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB; DFG grant GSC226/1) (R.Y.).
Data and resource availability
The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (Perez-Riverol et al., 2025) partner repository with the dataset identifiers PXD062418 (TOM20 IP data), PXD062420 (MAPL IP data), PXD062440 (TRABD IP data) and PXD062441 (TRABD siRNA data).
Special Issue
This article is part of the Special Issue ‘Cell Biology of Mitochondria’, guest edited by Ana J. Garcia-Saez and Heidi McBride. See related articles at https://journals.biologists.com/jcs/issue/138/9.
