Regulation of mitochondrial bioenergetic function by hydrogen sulfide. Part II: Pathophysiological and therapeutic aspects

Katalin Modis, Eelke M. Bos, Enrico Calzia, Harry van Goor, Ciro Coletta, Andreas Papapetropoulos, Mark R. Hellmich, Peter Radermacher, Frederic Bouillaud, Csaba Szabo*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

90 Citations (Scopus)

Abstract

Emerging work demonstrates the dual regulation of mitochondrial function by hydrogen sulfide (H2S), including, at lower concentrations, a stimulatory effect as an electron donor, and, at higher concentrations, an inhibitory effect on cytochrome C oxidase. In the current article, we overview the pathophysiological and therapeutic aspects of these processes. During cellular hypoxia/acidosis, the inhibitory effect of H2S on complex IV is enhanced, which may shift the balance of H2S from protective to deleterious. Several pathophysiological conditions are associated with an overproduction of H2S (e.g. sepsis), while in other disease states H2S levels and H2S bioavailability are reduced and its therapeutic replacement is warranted (e.g. diabetic vascular complications). Moreover, recent studies demonstrate that colorectal cancer cells up-regulate the H2S-producing enzyme cystathionine -synthase (CBS), and utilize its product, H2S, as a metabolic fuel and tumour-cell survival factor; pharmacological CBS inhibition or genetic CBS silencing suppresses cancer cell bioenergetics and suppresses cell proliferation and cell chemotaxis. In the last chapter of the current article, we overview the field of H2S-induced therapeutic suspended animation', a concept in which a temporary pharmacological reduction in cell metabolism is achieved, producing a decreased oxygen demand for the experimental therapy of critical illness and/or organ transplantation.

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Original languageEnglish
Pages (from-to)2123-2146
Number of pages24
JournalBritish Journal of Pharmacology
Volume171
Issue number8
DOIs
Publication statusPublished - Apr-2014

Keywords

  • mitochondrial electron transport
  • bioenergetics
  • 3-mercaptopyruvate sulfurtransferase
  • gasotransmitters
  • blood vessels
  • nitric oxide
  • superoxide
  • free radicals
  • cysteine
  • ischaemia
  • shock
  • suspended animation
  • ISCHEMIA-REPERFUSION INJURY
  • CYSTATHIONINE-BETA-SYNTHASE
  • GLUCOSE-INDUCED APOPTOSIS
  • NITRIC-OXIDE SYNTHASE
  • ANIMATION-LIKE STATE
  • IN-VITRO MODEL
  • ISCHEMIA/REPERFUSION INJURY
  • SUSPENDED ANIMATION
  • OXIDATIVE STRESS
  • COLON-CANCER

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