Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

  • Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.

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Author:Marten SziborORCiDGND, Rolf Schreckenberg, Zemfira GizatullinaORCiD, Eric DufourORCiD, Marion Wiesnet, Praveen K. DhandapaniORCiD, Grazyna Debska‐VielhaberORCiD, Juliana HeidlerORCiD, Ilka WittigORCiD, Tuula A. NymanORCiD, Ulrich Gärtner, Andrew R. Hall, Victoria Pell, Carlo ViscomiORCiD, Thomas KriegORCiD, Michael P. MurphyORCiDGND, Thomas BraunORCiDGND, Frank Norbert GellerichORCiDGND, Klaus‐Dieter SchlüterORCiDGND, Howard T. JacobsORCiD
Parent Title (English):Journal of cellular and molecular medicine
Place of publication:Hoboken, NJ
Document Type:Article
Date of Publication (online):2020/02/10
Date of first Publication:2020/02/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/12/05
Tag:adaptive cardiac remodelling; alternative oxidase; cardiac ischaemia‐reperfusion; electron transport chain; mouse; reactive oxygen species
Page Number:15
First Page:3534
Last Page:3548
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0