In the methanogenic pathway from CO2 and H2, low potential electrons for CO2 reduction are generated by a flavin-based electron branching reaction catalysed by heterodisulphide reductase (Hdr) in complex with [NiFe]-hydrogenase (Mvh). The F420-reducing [NiFe]-hydrogenase (Frh) provides electrons for the methane formation pathway via the electron carrier F420. The production of both [NiFe]-hydrogenases in Methanothermobacter marburgensis is strongly down-regulated under strictly nickel-limited conditions. The Frh reaction is replaced by a coupled reaction with [Fe]-hydrogenase (Hmd), and the role of Mvh is taken over by F420-dependent electron donating proteins (Elp). Thus, Hmd provides all electrons for the reducing metabolism under these nickel-limited conditions.