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Alternative oxidase...
Alternative oxidase-mediated respiration prevents lethal mitochondrial cardiomyopathy
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- Rajendran, Jayasimman (author)
- University of Helsinki,Folkhälsan Research Center
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- Purhonen, Janne (author)
- University of Helsinki,Folkhälsan Research Center
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- Tegelberg, Saara (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,University of Helsinki,Folkhälsan Research Center
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- Smolander, Olli Pekka (author)
- University of Helsinki
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- Mörgelin, Matthias (author)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Rozman, Jan (author)
- Helmholtz Zentrum München,German Center for Diabetes Research
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- Gailus-Durner, Valerie (author)
- Helmholtz Zentrum München
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- Fuchs, Helmut (author)
- Helmholtz Zentrum München
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- Hrabe de Angelis, Martin (author)
- Helmholtz Zentrum München,Technical University of Munich,German Center for Diabetes Research
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- Auvinen, Petri (author)
- University of Helsinki
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- Mervaala, Eero (author)
- University of Helsinki
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- Jacobs, Howard T. (author)
- University of Tampere,University of Helsinki
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- Szibor, Marten (author)
- University of Helsinki,University of Tampere
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- Fellman, Vineta (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Folkhälsan Research Center,Helsinki University Central Hospital
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- Kallijärvi, Jukka (author)
- Folkhälsan Research Center,University of Helsinki
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(creator_code:org_t)
- 2018-12-10
- 2018
- English.
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In: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 2018
- Related links:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
Subject headings
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- Alternative oxidase (AOX) is a non-mammalian enzyme that can bypass blockade of the complex III-IV segment of the respiratory chain (RC). We crossed a Ciona intestinalis AOX transgene into RC complex III (cIII)-deficient Bcs1lp.S78G knock-in mice, displaying multiple visceral manifestations and premature death. The homozygotes expressing AOX were viable, and their median survival was extended from 210 to 590 days due to permanent prevention of lethal cardiomyopathy. AOX also prevented renal tubular atrophy and cerebral astrogliosis, but not liver disease, growth restriction, or lipodystrophy, suggesting distinct tissue-specific pathogenetic mechanisms. Assessment of reactive oxygen species (ROS) production and damage suggested that ROS were not instrumental in the rescue. Cardiac mitochondrial ultrastructure, mitochondrial respiration, and pathological transcriptome and metabolome alterations were essentially normalized by AOX, showing that the restored electron flow upstream of cIII was sufficient to prevent cardiac energetic crisis and detrimental decompensation. These findings demonstrate the value of AOX, both as a mechanistic tool and a potential therapeutic strategy, for cIII deficiencies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- BCS1L
- complex III
- GRACILE syndrome
- mitochondrial disorder
- respiratory chain
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Rajendran, Jayas ...
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Purhonen, Janne
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Tegelberg, Saara
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Smolander, Olli ...
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Mörgelin, Matthi ...
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Rozman, Jan
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Gailus-Durner, V ...
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Fuchs, Helmut
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Hrabe de Angelis ...
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Auvinen, Petri
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Mervaala, Eero
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Jacobs, Howard T ...
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Szibor, Marten
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Fellman, Vineta
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Kallijärvi, Jukk ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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EMBO Molecular M ...
- By the university
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Lund University