H2O2 Signalling Pathway: A Possible Bridge between Insulin Receptor and Mitochondria

Abstract

This review is focused on the mechanistic aspects of the insulin-induced H 2 O 2 signalling pathway in neurons and the molecules affecting it, which act as risk factors for developing central insulin resistance. Insulin-induced H 2 O 2 promotes insulin receptor activation and the mitochondria act as the insulin-sensitive H 2 O 2 source, providing a direct molecular link between mitochondrial dysfunction and irregular insulin receptor activation. In this view, the accumulation of dysfunctional mitochondria during chronological ageing and Alzheimer's disease (AD) is a risk factor that may contribute to the development of dysfunctional cerebral insulin receptor signalling and insulin resistance. Due to the high significance of insulin-induced H 2 O 2 for insulin receptor activation, oxidative stress-induced upregulation of antioxidant enzymes, e.g., in AD brains, may represent another risk factor contributing to the development of insulin resistance. As insulin-induced H 2 O 2 signalling requires fully functional mitochondria, pharmacological strategies based on activating mitochondria biogenesis in the brain are central to the treatment of diseases associated with dysfunctional insulin receptor signalling in this organ.

A mitochondrial-targetable dual functional near-infrared fluorescent probe to monitor pH and H2O2 in living cells and mice

“…18 Abnormal levels of pH and H 2 O 2 in the mitochondria are associated with various diseases like cancer, Alzheimer's disease and cardiovascular diseases. [19][20][21][22] Thus, determination of mitochondrial changes in pH and level of H 2 O 2 is of great importance and could provide new insights into the key functions of mitochondria under both physiological and pathological conditions.…”