期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 9, 页码 3530-3535出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1812941116
关键词
MPC; retinal degeneration; mitochondrial metabolism; pyruvate; glutamine
资金
- NIH [EY026030, EY06641, EY017863, EY025291]
- Brightfocus Foundation
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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