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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls

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Saari, Sina [1, 2] ; Garcia, Geovana S. [3] ; Bremer, Katharina [1, 2] ; Chioda, Marina M. [3] ; Andjelkovic, Ana [1, 2] ; Debes, Paul V. [4, 5] ; Nikinmaa, Mikko [4] ; Szibor, Marten [1, 2] ; Dufour, Eric [1, 2] ; Rustin, Pierre [6, 7] ; Oliveira, Marcos T. [3] ; Jacobs, Howard T. [1, 8, 2]
Total Authors: 12
[1] Univ Tampere, Tampere Univ Hosp, FI-33014 Tampere - Finland
[2] Univ Tampere, BioMediTech Inst, Fac Med & Life Sci, FI-33014 Tampere - Finland
[3] Univ Estadual Paulista, Fac Ciencias Agr & Vet, Dept Tecnol, BR-14884900 Jaboticabal, SP - Brazil
[4] Univ Turku, Dept Biol, FI-20014 Turku - Finland
[5] Univ Helsinki, Fac Biol & Environm Sci, FI-00014 Helsinki - Finland
[6] Hop Robert Debre, INSERM, UMR1141, 48 Blvd Serurier, F-75019 Paris - France
[7] Univ Paris 07, Fac Med Denis Diderot, Paris - France
[8] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki - Finland
Total Affiliations: 8
Document type: Review article
Web of Science Citations: 6

The alternative respiratory chain (aRC), comprising the alternative NADH dehydrogenases (NDX) and quinone oxidases (AOX), is found in microbes, fungi and plants, where it buffers stresses arising from restrictions on electron flow in the oxidative phosphorylation system. The aRC enzymes are also found in species belonging to most metazoan phyla, including some chordates and arthropods species, although not in vertebrates or in Drosophila. We postulated that the aRC enzymes might be deployed to alleviate pathological stresses arising from mitochondria! dysfunction in a wide variety of disease states. However, before such therapies can be contemplated, it is essential to understand the effects of aRC enzymes on cell metabolism and organismal physiology. Here we report and discuss new findings that shed light on the functions of the aRC enzymes in animals, and the unexpected benefits and detriments that they confer on model organisms. In Clone intestinalis, the aRC is induced by hypoxia and by sulfide, but is unresponsive to other environmental stressors. When expressed in Drosophila, AOX results in impaired survival under restricted nutrition, in addition to the previously reported male reproductive anomalies. In contrast, it confers cold resistance to developing and adult flies, and counteracts cell signaling defects that underlie developmental dysmorphologies. The aRC enzymes may also influence life span and stress resistance more generally, by eliciting or interfering with hormetic mechanisms. In sum, their judicious use may lead to major benefits in medicine, but this will require a thorough characterization of their properties and physiological effects. (AU)

FAPESP's process: 14/02253-6 - Investigating the metabolic alterations caused by the transgenic expression of the mitochondrial alternative oxidase of Ciona intestinalis in Drosophila melanogaster
Grantee:Marcos Túlio de Oliveira
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 15/02174-1 - Carbohydrate restriction effect on AOX flies development
Grantee:Marina Minari Chioda
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/00013-3 - Temperature variation effects on AOX flies development
Grantee:Geovana Siqueira Garcia
Support type: Scholarships in Brazil - Scientific Initiation