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Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3530-3535. doi: 10.1073/pnas.1812941116. Epub 2019 Feb 11.

Loss of MPC1 reprograms retinal metabolism to impair visual function.

Author information

1
Department of Ophthalmology, West Virginia University, Morgantown, WV 26506.
2
Department of Biochemistry, West Virginia University, Morgantown, WV 26506.
3
Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107.
4
Department of Biochemistry, University of Washington, Seattle, WA 98109.
5
Department of Ophthalmology, University of Washington, Seattle, WA 98109.
6
Eye Research Institute, Oakland University, Rochester, MI 48309.
7
Department of Ophthalmology, West Virginia University, Morgantown, WV 26506; jianhai.du@wvumedicine.org.

Abstract

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 13C tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization.

KEYWORDS:

MPC; glutamine; mitochondrial metabolism; pyruvate; retinal degeneration

PMID:
30808746
PMCID:
PMC6397593
[Available on 2019-08-11]
DOI:
10.1073/pnas.1812941116
[Indexed for MEDLINE]

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