This AOP describes how inhibitors of complex I of the mitochondrial electron transport chain (ETC) can affect proximal tubule vectorial transport. This can lead to Fanconi syndrome (FS) as an adverse outcome, via a depletion of ATP leading to decreased vectorial transport. Indeed, chemicals that target complex I cause a large disturbance in the supply of electrons to the ETC, resulting in decreased efficiency of mitochondrial respiration. Since this process is responsible for the production of most of the ATP in mammalian cells, this likely results in an impairment of transport by ATP-dependent transporters such as the sodium/potassium ATPase. This leads to a decrease in downstream secondary active transports of water and solutes, which is the main characteristic of FS. The primary organism targeted with this AOP is humans, with potential applicability to other mammalian species. Vrije Universit is working in EU-ToxRisk case study 4 and the renal exploratory study on addressing data gaps, in particular, to produce data to be used in modeling of a quantitative AOP.