The serine/threonine kinase Akt has been shown to mediate the anti-apoptotic activity through hexokinase(HK)–mitochondria interaction. We previously reported that Akt activation in retinal rod photoreceptor cells is mediated through the light-dependent insulin receptor (IR)/PI3K pathway. Our data indicate that lightinduced activation of IR/PI3K/Akt results in the translocation of HK-II to mitochondria. We also found that PHLPPL, a serine/threonine phosphatase, enhanced the binding of HK-II to mitochondria. We found a mitochondrial targeting signal in PHLPPL and our study suggests that Akt translocation to mitochondria could be mediated through PHLPPL. Our results suggest that the light-dependent IR/PI3K/Akt pathway regulates hexokinase– mitochondria interaction in photoreceptors. Down-regulation of IR signaling has been associated with ocular diseases of retinitis pigmentosa, diabetic retinopathy, and Leber Congenital Amaurosis-type 2, and agents that enhance the binding interaction between hexokinase and mitochondria may have therapeutic potential against these ocular diseases.
- Insulin receptor
- Phosphoinositide 3-kinase
- Glycogen synthase kinase
Rajala, A., Gupta, V. K., Anderson, R. E., & Rajala, R. V. S. (2013). Light activation of the insulin receptor regulates mitochondrial hexokinase. A possible mechanism of retinal neuroprotection. Mitochondrion, 13(6), 566-576. https://doi.org/10.1016/j.mito.2013.08.005