Houman Ashrafian, Gabor Czibik, Mohamed Bellahcene, Dunja Aksentijević, Anthony C Smith, Sarah J Mitchell, Michael S Dodd, Jennifer Kirwan, Jonathan J Byrne, Christian Ludwig, Henrik Isackson, Arash Yavari, Nicolaj B Støttrup, Hussain Contractor, Thomas J Cahill, Natasha Sahgal, Daniel R Ball, Rune I D Birkler, Iain Hargreaves, Daniel A Tennant, John Land, Craig A Lygate, Mogens Johannsen, Rajesh K Kharbanda, Stefan Neubauer, Charles Redwood, Rafael de Cabo, Ismayil Ahmet, Mark Talan, Ulrich L Günther, Alan J Robinson, Mark R Viant, Patrick J Pollard, Damian J Tyler, Hugh Watkins
The citric acid cycle (CAC) metabolite fumarate has been proposed to be cardioprotective; however, its mechanisms of action remain to be determined. To augment cardiac fumarate levels and to assess fumarate's cardioprotective properties, we generated fumarate hydratase (Fh1) cardiac knockout (KO) mice. These fumarate-replete hearts were robustly protected from ischemia-reperfusion injury (I/R). To compensate for the loss of Fh1 activity, KO hearts maintain ATP levels in part by channeling amino acids into the CAC...
March 7, 2012: Cell Metabolism