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Kanaan 2017 Redox Biol

From Bioblast
Publications in the MiPMap
Kanaan GN, Ichim B, Gharibeh L, Maharsy W, Patten DA, Xuan JY, Reunov A, Marshall P, Veinot J, Menzies K, Nemer M, Harper ME (2017) Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies. Redox Biol 14:509-21.

ยป PMID: 29101900 Open Access

Kanaan GN, Ichim B, Gharibeh L, Maharsy W, Patten DA, Xuan JY, Reunov A, Marshall P, Veinot J, Menzies K, Nemer M, Harper ME (2017) Redox Biol

Abstract: Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies. โ€ข Keywords: Cardiac hypertrophy, Cardiac metabolism, Human heart, Mitochondria, Oxidative stress, Redox โ€ข Bioblast editor: Kandolf G โ€ข O2k-Network Lab: CA Ottawa Harper ME


Labels: MiParea: Respiration, mt-Structure;fission;fusion 


Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS  Pathway: N, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2018-01