title: 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.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Katalin
authors.initials: K
authors.lastname: Módis
authors.forename: Eelke M
authors.initials: EM
authors.lastname: Bos
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Ciro
authors.initials: C
authors.lastname: Coletta
authors.forename: Andreas
authors.initials: A
authors.lastname: Papapetropoulos
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellmich
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bouillaud
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
mesh_terms: D000818:Animals; D048909:Diabetes Complications / Q000503:physiopathology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D064426:Gasotransmitters / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006605:Hibernation / Q000502:physiology; D006801:Humans; D006862:Hydrogen Sulfide / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology; D012769:Shock / Q000503:physiopathology
chemical_list: D064426:Gasotransmitters; D006862:Hydrogen Sulfide
keywords: 3-mercaptopyruvate sulfurtransferase; bioenergetics; blood vessels; cysteine; free radicals; gasotransmitters; ischaemia; mitochondrial electron transport; nitric oxide; shock; superoxide; suspended animation