Abstract 2333 Unlocking the Potential of the Mammalian Electron Transport Chain

The mitochondrial electron transport chain (ETC) is a series of electron transfer reactions that support multifaceted bioenergetic, biosynthetic, and signaling pathways. In textbook drawings of the mammalian ETC, electrons enter at complexes I and II, are carried to complex III by ubiquinone, and deposited on the terminal electron acceptor oxygen via complex IV activity. Hypoxia (low oxygen) and/or mutations to ETC complexes disrupt this circuit, impeding mitochondrial functions and causing severe disease. We recently published that mammalian mitochondria use fumarate as an electron acceptor in hypoxic environments to sustain ETC-dependent functions such as pyrimidine biosynthesis (Spinelli et al., Science, 2021). Surprisingly, this reaction is restricted to a subset of tissues, although the mechanism underlying this tissue-specificity is still unknown. This seminar will elucidate mechanism underlying the tissue-specificity of mammalian ETC circuits. This work was generously supported by the Searle Scholar's Program, Smith Family Foundation, American Federation for Aging Research, and the WorcesterFoundation for Biomedical Research.