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LETTER

H2S and O2 sensing

Oxygen-sensing cells in the carotid body, blood vessels, airways,
and adrenal gland initiate vital homeostatic responses to hypoxia
and hypoxemia. Inappropriate activity of these cells is asso-
ciated with a variety of pathophysiologies, but despite intense
research and obvious clinical applicability, there is no consensus
regarding the oxygen sensor that directly couples oxygen avail-
ability to the eventual physiological response.
In the recent article “H2S mediates O2 sensing by the carotid

body,” Peng et al. (1) showed that the hypoxic responses of ca-
rotid bodies were significantly decreased in mice lacking cys-
tathionine γ lyase (CSE), one of the enzymes involved in H2S
biosynthesis. They also provided evidence for H2S-mediated
hypoxic responses in both chemoreceptor and adrenal chro-
maffin cells. The authors state in their introduction that “given
that carotid bodies are peripheral organs and that H2S is redox
active, we hypothesized that CSE-derived H2S plays a role in
hypoxic sensing by the carotid body”; in their discussion, they
state that the “present study established a physiological role for
H2S generated by CSE in mediating hypoxic sensing” (1). This
leads the reader to believe that the authors have identified
a novel oxygen-sensing mechanism. Actually, this is not a novel
hypothesis (1).
Peng et al. (1) failed to cite that the concept of H2S-mediated

O2 sensing was first proposed by us (2) in 2006. In our model,
tissue H2S concentration is established by the simple balance
between constitutive production and oxygen-dependent in-
activation. In subsequent work (reviewed in ref. 3), we showed
that H2S and hypoxic responses were identical and that the
latter could be blocked by inhibitors of H2S biosynthesis. We
measured H2S production in many living tissues in real time

and showed that H2S concentration was inversely related to
tissue PO2 at PO2s encountered during hypoxia. We also showed
that H2S was readily consumed by mitochondria, also at physi-
ologically relevant Po2s. Clearly, there was substantial evidence
for H2S-mediated O2 sensing before the study by Peng et al. (1).
Furthermore, Peng et al. (1) failed to acknowledge that

we had previously shown H2S-mediated O2 sensing in fish
chromaffin cells (4) and that these cells are homologous to the
mammalian cells. In fact, the only reference to any of our papers
was this brief sentence: “It is interesting to note that H2S has
been demonstrated to mediate O2 sensing by the trout gill
chemoreceptors, indicating that it is an ancient well-
conserved system across phyla” (1). Actually, this is more than
a phylogenetic curiosity. Not only did we present evidence for-
a H2S-mediated O2 sensing mechanism, we clearly pointed out
that these chemoreceptors are homologous to, and the ante-
cedent of, mammalian chemoreceptors (5). In our opinion, our
work established the precedent for H2S-mediated O2-sensing
mechanisms in both chemoreceptors and chromaffin cells.

Kenneth R. Olsona,1 and Steve F. Perryb
aDepartment of Physiology, Indiana University School of Medicine,
South Bend, IN 46617; and bDepartment of Biology, University of
Ottawa, Ottawa, ON, Canada K1N 6N5

1. Peng YJ, et al. (2010) H2S mediates O2 sensing in the carotid body. Proc Natl Acad Sci
USA 107:10719–10724.

2. Olson KR, et al. (2006) Hydrogen sulfide as an oxygen sensor/transducer in vertebrate
hypoxic vasoconstriction and hypoxic vasodilation. J Exp Biol 209:4011–4023.

3. Olson KR, Whitfield NL (2010) Hydrogen sulfide and oxygen sensing in the cardio-
vascular system. Antioxid Redox Signal 12:1219–1234.

4. Perry SF, McNeill B, Elia E, Nagpal A, Vulesevic B (2009) Hydrogen sulfide stimulates
catecholamine secretion in rainbow trout (Oncorhynchus mykiss). Am J Physiol Regul
Integr Comp Physiol 296:R133–R140.

5. Olson KR, et al. (2008) Hydrogen sulfide as an oxygen sensor in trout gill chemo-
receptors. Am J Physiol Regul Integr Comp Physiol 295:R669–R680.

Author contributions: K.R.O. and S.F.P. wrote the paper.

The authors declare no conflict of interest.
1To whom correspondence should be addressed. E-mail: olson.1@nd.edu.

www.pnas.org/cgi/doi/10.1073/pnas.1009210107 PNAS | September 14, 2010 | vol. 107 | no. 37 | E141

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