| Literature DB >> 30808746 |
Allison Grenell1,2, Yekai Wang1,2, Michelle Yam1,2, Aditi Swarup3, Tanya L Dilan1,2, Allison Hauer1,2, Jonathan D Linton4,5, Nancy J Philp3, Elizabeth Gregor1,2, Siyan Zhu1,2, Quan Shi1, Joseph Murphy1,2, Tongju Guan1,2, Daniel Lohner1,2, Saravanan Kolandaivelu1,2, Visvanathan Ramamurthy1,2, Andrew F X Goldberg6, James B Hurley4,5, Jianhai Du7,2.
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.Entities:
Keywords: MPC; glutamine; mitochondrial metabolism; pyruvate; retinal degeneration
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Year: 2019 PMID： 30808746 PMCID： PMC6397593 DOI： 10.1073/pnas.1812941116
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779