Hydrogen sulfide (H₂S) can be consumed by both invertebrates and vertebrates as an inorganic substrate. The pathway metabolizing H₂S probably involves three mitochondrial enzymes, one of which is sulfide-quinone oxidoreductase (SQR), known as sulfide-quinone reductase-like protein (SQRDL) in vertebrates. Evidence from fission yeast suggests that SQR might have a role in regulating sulfide levels in the cell. Regulation might be essential for H₂S to act as a gaseous transmitter (gasotransmitter). The brain is an organ with high activity of gasotransmitters, like nitric oxide (NO) and H₂S, which are known to affect synaptic transmission. In this study, we provide evidence that SQRDL is expressed in the mammalian brain. Real-time polymerase chain reaction (PCR) showed an increase in the number of Sqrdl transcripts in the brain with increasing age. Cellular fractionation and subsequent analysis by Western blotting indicated that the protein is located in mitochondria, which is the site of sulfide consumption in the cell. With an immunohistochemical approach, we demonstrated that the SQRDL protein is expressed in neurons, oligodendrocytes, and endothelial cells. Taken together, our data suggest that brain tissue harbors the machinery required for local regulation of sulfide levels.