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- Loss of MPC1 reprograms retinal metabolism to impair visual function.
Loss of MPC1 reprograms retinal metabolism to impair visual function.
Citation | “Loss Of Mpc1 Reprograms Retinal Metabolism To Impair Visual Function.”. Proceedings Of The National Academy Of Sciences Of The United States Of America, pp. 3530-3535. . |
Center | University of Washington |
Author | Allison Grenell, Yekai Wang, Michelle Yam, Aditi Swarup, Tanya L Dilan, Allison Hauer, Jonathan D Linton, Nancy J Philp, Elizabeth Gregor, Siyan Zhu, Quan Shi, Joseph Murphy, Tongju Guan, Daniel Lohner, Saravanan Kolandaivelu, Visvanathan Ramamurthy, Andrew F X Goldberg, James B Hurley, Jianhai Du |
Keywords | MPC, glutamine, mitochondrial metabolism, pyruvate, retinal degeneration |
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 C tracers, we found that MPC1 is required for cytosolic reducing power maintenance, glutamine/glutamate metabolism, and flexibility in fuel utilization. |
Year of Publication |
2019
|
Journal |
Proceedings of the National Academy of Sciences of the United States of America
|
Volume |
116
|
Issue |
9
|
Number of Pages |
3530-3535
|
Date Published |
12/2019
|
ISSN Number |
1091-6490
|
DOI |
10.1073/pnas.1812941116
|
Alternate Journal |
Proc. Natl. Acad. Sci. U.S.A.
|
PMID |
30808746
|
PMCID |
PMC6397593
|
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