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Two‐photon AMPK and ATP imaging reveals the bias between rods and cones in glycolysis utility
Author(s) -
He Jiazhou,
Yamamoto Masamichi,
Sumiyama Kenta,
Konagaya Yumi,
Terai Kenta,
Matsuda Michiyuki,
Sato Shinya
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202101121r
Subject(s) - ampk , glycolysis , microbiology and biotechnology , oxidative phosphorylation , retinal , retina , chemistry , biology , protein kinase a , biophysics , phosphorylation , biochemistry , metabolism , neuroscience
Abstract In vertebrates, retinal rod and cone photoreceptor cells rely significantly on glycolysis. Lactate released from photoreceptor cells fuels neighboring retinal pigment epithelium cells and Müller glial cells through oxidative phosphorylation. To understand this highly heterogeneous metabolic environment around photoreceptor cells, single‐cell analysis is needed. Here, we visualized cellular AMP‐activated protein kinase (AMPK) activity and ATP levels in the retina by two‐photon microscopy. Transgenic mice expressing a hyBRET‐AMPK biosensor were used for measuring the AMPK activity. GO‐ATeam2 transgenic mice were used for measuring the ATP level. Temporal metabolic responses were successfully detected in the live retinal explants upon drug perfusion. A glycolysis inhibitor, 2‐deoxy‐ d ‐glucose (2‐DG), activated AMPK and reduced ATP. These effects were clearly stronger in rods than in cones. Notably, rod AMPK and ATP started to recover at 30 min from the onset of 2‐DG perfusion. Consistent with these findings, ex vivo electroretinogram recordings showed a transient slowdown in rod dim flash responses during a 60‐min 2‐DG perfusion, whereas cone responses were not affected. Based on these results, we propose that cones surrounded by highly glycolytic rods become less dependent on glycolysis, and rods also become less dependent on glycolysis within 60 min upon the glycolysis inhibition.