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

Abstract
Emerging work demonstrates the dual regulation of mitochondrial function by hydrogen sulfide (H2 S), 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 H2 S on complex IV is enhanced, which may shift the balance of H2 S from protective to deleterious. Several pathophysiological conditions are associated with an overproduction of H2 S (e.g. sepsis), while in other disease states H2 S levels and H2 S 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 H2 S-producing enzyme cystathionine β-synthase (CBS), and utilize its product, H2 S, 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 H2 S-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.
AuthorsKatalin Módis, Eelke M Bos, Enrico Calzia, Harry van Goor, Ciro Coletta, Andreas Papapetropoulos, Mark R Hellmich, Peter Radermacher, Frédéric Bouillaud, Csaba Szabo
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 171 Issue 8 Pg. 2123-46 (Apr 2014) ISSN: 1476-5381 [Electronic] England
PMID23991749 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
Copyright© 2013 The British Pharmacological Society.
Chemical References
  • Gasotransmitters
  • Hydrogen Sulfide
Topics
  • Animals
  • Diabetes Complications (physiopathology)
  • Energy Metabolism (drug effects, physiology)
  • Gasotransmitters (adverse effects, metabolism, pharmacology, physiology, therapeutic use)
  • Hibernation (physiology)
  • Humans
  • Hydrogen Sulfide (adverse effects, metabolism, pharmacology, therapeutic use)
  • Mitochondria (metabolism, physiology)
  • Neoplasms (physiopathology)
  • Shock (physiopathology)

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