FAM136A is an essential chaperone for mitochondrial membrane protein biogenesis

Authors

Ernst, M., Zhang, J., Xu, H., Ma, A., Boegeholz, L. A. K., Szabo, M., Wang, T.-Y., Chou, T.-F., Guna, A., Voorhees, R. M.

Abstract

The metabolic and signaling function of mitochondria rely on a network of chaperones within the inner membrane space (IMS) that regulate the biogenesis of nascent mitochondrial proteins. Using a genome wide CRISPRi screen we found that in human cells FAM136A is required for biogenesis of all three voltage-dependent anion channel (VDAC) paralogs, an abundant and essential family of beta-barrel metabolite transporters in the outer mitochondrial membrane (OM). FAM136A is a ubiquitously expressed essential gene, that is conserved in metazoa and plants. Using a combination of experiments in human cells and in vitro reconstitution, we determined that FAM136A associates with unfolded VDACs in the IMS; solubilizes nascent VDAC through a direct interaction; and facilitates insertion of VDAC into the OM. FAM136A also binds and chaperones a subset of alpha-helical subunits of the electron transport chain. We therefore conclude that FAM136A is an IMS-resident chaperone, necessary and sufficient to maintain nascent membrane proteins in a folding-competent state to mediate their integration into the bilayer.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 05 Aug 2026.

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