To obtain insight into the molecular mechanism of FH intracellular function in hTERT-RPE1 cells, we analyzed the interactome of FH via its immunoprecipitation followed by MS-based analysis. We found that FH interacts with essential components of the ubiquitin-proteasomal pathway (UPS) as well as with RB1/E2F signalling in a complement-pathway independent manner. Moreover, we found, that FH silencing affects mRNA levels of the E3 Ubiquitin-Protein Ligase Parkin and PTEN induced putative kinase (Pink1), both of them are associated with UPS. As inhibition of mTORC1 has been previoulsy shown to result in increased overall protein degradation via UPS and as FH mRNA and protein levels were shown to be affected by inhibition of UPS, our data stress a potential regulatory link between endogenous FH activity and UPS.