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Jianhai Du, Jonathan Linton, James Hurley; Loss of mitochondrial pyruvate carrier 1 in rod photoreceptors impairs mitochondrial intermediary metabolism. Invest. Ophthalmol. Vis. Sci. 2017;58(8):593.
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Photoreceptors are active in both aerobic glycolysis and mitochondrial oxidative metabolism. Mitochondrial pyruvate carrier (MPC) transports pyruvate produced by glycolysis into mitochondria. We have generated mice with rod photoreceptor-specific deletion of MPC1 and have used 13C tracers to study the role of MPC in regulating retinal mitochondrial metabolism.
MPC1 flox/flox mice were crossed with rod photoreceptor cre mice (Rhodopsin-iCre) to generate mice with rod specific deletion of MPC1 (RS MPC-/-). Mouse retinas were incubated with 13C glucose and labeled metabolites were measured by GC-MS.
Pyruvate accumulates about 3.5 fold higher than normal in RS MPC -/- retinas than the control littermates but the level of lactate remains unchanged. Pyruvate can be transaminated into alanine. We found that labeled alanine in RS MPC -/- is 1.5 fold higher than in controls. Remarkably, mitochondrial a-ketoglutarate and glutamate decrease. M5 glutamate is 30% and labeled glutamine is 40% of their levels in control retinas. M3 malate and aspartate accumulate to higher than normal levels in RS MPC -/-. M3 citrate increases while flux into M4 and M6 citrate decreases.
Loss of mitochondrial pyruvate carrier 1 in rod photoreceptors disrupts mitochondrial intermediary metabolism. Aspartate and malate accumulate at the expense of glutamate and glutamine.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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