Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part I. Biochemical and physiological mechanisms

Csaba Szabo, Céline Ransy, Katalin Módis, Mireille Andriamihaja, Baptiste Murghes, Ciro Coletta, Gabor Olah, Kazunori Yanagi, Frédéric Bouillaud

Research output: Contribution to journalReview articlepeer-review

190 Scopus citations

Abstract

Until recently, hydrogen sulfide (H2S) was exclusively viewed a toxic gas and an environmental hazard, with its toxicity primarily attributed to the inhibition of mitochondrial Complex IV, resulting in a shutdown of mitochondrial electron transport and cellular ATP generation. Work over the last decade established multiple biological regulatory roles of H2S, as an endogenous gaseous transmitter. H2S is produced by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). In striking contrast to its inhibitory effect on Complex IV, recent studies showed that at lower concentrations, H2S serves as a stimulator of electron transport in mammalian cells, by acting as a mitochondrial electron donor. Endogenous H2S, produced by mitochondrially localized 3-MST, supports basal, physiological cellular bioenergetic functions; the activity of this metabolic support declines with physiological aging. In specialized conditions (calcium overload in vascular smooth muscle, colon cancer cells), CSE and CBS can also associate with the mitochondria; H2S produced by these enzymes, serves as an endogenous stimulator of cellular bioenergetics. The current article overviews the biochemical mechanisms underlying the stimulatory and inhibitory effects of H2S on mitochondrial function and cellular bioenergetics and discusses the implication of these processes for normal cellular physiology. The relevance of H2S biology is also discussed in the context of colonic epithelial cell physiology: colonocytes are exposed to high levels of sulfide produced by enteric bacteria, and serve as a metabolic barrier to limit their entry into the mammalian host, while, at the same time, utilizing it as a metabolic 'fuel'.

Original languageEnglish (US)
Pages (from-to)2099-2122
Number of pages24
JournalBritish Journal of Pharmacology
Volume171
Issue number8
DOIs
StatePublished - Apr 2014

Keywords

  • 3-mercaptopyruvate sulfurtransferase
  • bioenergetics
  • blood vessels
  • cysteine
  • cytochrome c oxidase
  • free radicals
  • gasotransmitters
  • mitochondrial electron transport
  • nitric oxide
  • superoxide

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)

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