PINK1 stabilizes RMDN3-VAPB interaction without altering the landscape of mito-ER contact sites

Authors

Rühmkorf, A., Zorn, A., Duschek, J., Herrera, M. G., Levantovsky, S. K., Feederle, R., Moschogiannaki, F., Winklhofer, K. F., Behrends, C., Harbauer, A. B.

Abstract

Mitochondria-ER contact sites (MERCS) have emerged as central hubs of organellar biology, participating in the exchange of lipids, Ca2+ and even protein precursors. During mitochondrial dysfunction, the contact between the ER-resident protein VAPB and the outer mitochondrial membrane protein RMDN3 (PTPIP51) increases, yet the mechanism stabilizing this connection despite ongoing mitophagy remains to be determined. Here we develop a splitAPEX2 based proximity biotinylation tool to assess the interaction of VAPB and RMDN3. We determine that activation of the mitochondrial depolarization-induced kinase PINK1 leads to phosphorylation of RMDN3 at T160, which is necessary to increase the interaction with VAPB in the presence of mitochondrial depolarization. Mass Spectrometric analysis of the RMDN3-VAPB MERCS proteome reveals that these contacts also include peroxisomal proteins and that the proteomic composition remains stable during mitochondrial depolarization.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Jul 2026.

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