Light activation of the insulin receptor regulates mitochondrial hexokinase. A possible mechanism of retinal neuroprotection

Ammaji Rajala, Vivek K. Gupta, Robert E. Anderson, Raju V. S. Rajala

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)566-576
Number of pages11
JournalMitochondrion
Volume13
Issue number6
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Insulin receptor
  • Phosphoinositide 3-kinase
  • Glycogen synthase kinase
  • Neuroprotection
  • Mitochondria
  • Hexokinase

Fingerprint Dive into the research topics of 'Light activation of the insulin receptor regulates mitochondrial hexokinase. A possible mechanism of retinal neuroprotection'. Together they form a unique fingerprint.

  • Cite this