Title : Monoamine oxidase-A is a novel driver of stress-induced premature senescence through inhibition of parkin-mediated mitophagy.

Pub. Date : 2018 Oct

PMID : 30003648






4 Functional Relationships(s)
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1 The mitochondrial enzyme monoamine oxidase-A (MAO-A) is a relevant source of ROS in the heart through the formation of H2 O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin. Reactive Oxygen Species monoamine oxidase A Homo sapiens
2 The mitochondrial enzyme monoamine oxidase-A (MAO-A) is a relevant source of ROS in the heart through the formation of H2 O2 derived from the degradation of its main substrates, norepinephrine (NE) and serotonin. Reactive Oxygen Species monoamine oxidase A Homo sapiens
3 Using cardiomyoblasts and primary cardiomyocytes, we demonstrate that chronic MAO-A activation mediated by synthetic (tyramine) and physiological (NE) substrates induces ROS-dependent DNA damage response, activation of cyclin-dependent kinase inhibitors p21cip , p16ink4a , and p15ink4b and typical features of senescence such as cell flattening and SA-beta-gal activity. Reactive Oxygen Species monoamine oxidase A Homo sapiens
4 Moreover, we observe that ROS produced by MAO-A lead to the accumulation of p53 in the cytosol where it inhibits parkin, an important regulator of mitophagy, resulting in mitochondrial dysfunction. Reactive Oxygen Species monoamine oxidase A Homo sapiens