Abstract:
Hydrogen sulfide (H2S) is a gaseous molecule which can act as an inorganic substrate for
energy production. On the other hand, high concentrations of H2S can act as a poison by
inhibiting cellular respiration, but the mechanism of H2S clearance when respiration is inhibited
is unclear. Sulfide quinone oxidoreductase (SQOR) catalyzes the initial step of the
mitochondrial sulfide oxidation pathway by oxidizing H2S to a persulfide and transferring the
electrons to coenzyme Q (CoQ). In this study, we have investigated how competition between
SQOR and other enzymes for use of the CoQ pool modulates the capacity for H2S clearance.
Monitoring the oxygen consumption rate by the electron transport chain, we found that cells
with compromised complex I or complex II activity exhibit enhanced or decreased ability to
clear H2S, respectively, suggesting that both complexes are significant modulators of SQOR
activity. When complex IV-dependent respiration was inhibited, complex II was found to work
in reverse, oxidizing CoQH2 to CoQ by using fumarate as an alternate electron acceptor and
increasing sulfide oxidation capacity. We also demonstrated that the malate aspartate shuttle
plays an important role in providing fumarate to sustain SQOR activity under these conditions.
Complex II-dependent SQOR activity could be a mechanism by which H2S acts as a protective
agent during reperfusion following ischemia, attenuating injury. In related studies, we
investigated an altered response to H2S following knock down of persulfide dioxygenase
(ETHE1), the second enzyme in the mitochondrial sulfide oxidation pathway. Finally,
modulation of cystathionine beta synthase activity by select metabolites was probed
