Flexibility in the electron transport chain

The electron transport chain (ETC) is a series of reduction and oxidation reactions embedded in the inner mitochondrial membrane that sustain critical mitochondrial functions. We recently discovered that mammalian tissues can utilize fumarate as a terminal electron acceptor to support some of these crucial mitochondrial functions such as de novo pyrimidine biosynthesis (Spinelli et al., Science. 2021). The ability to utilize fumarate as an electron acceptor is tissue-specific. We seek to elucidate the mechanisms underlying tissue-specificity of flexibility in the mammalian ETC for this and other pathways.