Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 9, Pages 3530-3535Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1812941116
Keywords
MPC; retinal degeneration; mitochondrial metabolism; pyruvate; glutamine
Categories
Funding
- NIH [EY026030, EY06641, EY017863, EY025291]
- Brightfocus Foundation
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Glucose metabolism in vertebrate retinas is dominated by aerobic glycolysis (the Warburg Effect), which allows only a small fraction of glucose-derived pyruvate to enter mitochondria. Here, we report evidence that the small fraction of pyruvate in photoreceptors that does get oxidized by their mitochondria is required for visual function, photoreceptor structure and viability, normal neuron-glial interaction, and homeostasis of retinal metabolism. The mitochondrial pyruvate carrier (MPC) links glycolysis and mitochondrial metabolism. Retina-specific deletion of MPC1 results in progressive retinal degeneration and decline of visual function in both rod and cone photoreceptors. Using targeted-metabolomics and C-13 tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization.
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