Rod Outer Segment Retinol Formation Is Independent of Abca4, Arrestin, Rhodopsin Kinase, and Rhodopsin Palmitylation

Blakeley, Lorie R.; Chen, Chunhe; Chen, Ching‐Kang; Chen, Jeannie; Crouch, Rosalie K.; Travis, Gabriel H.; Koutalos, Yiannis

doi:10.1167/iovs.10-6694

Cited by 19 publications

(28 citation statements)

References 58 publications

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“…The measurements estimate that 0.8 -0.9 of all-transretinal is converted to retinol in the outer segment of metabolically intact rods, in close agreement with biochemical measurements from extracts of whole isolated retinas (12,16) ] ratio is achieved when metabolic substrate is not limiting and when all pathways that can generate NADPH are operational. The ratio decreases when metabolic substrates become limiting or when some pathways are inhibited.…”

Section: Discussionsupporting

confidence: 78%

“…Somewhat lower values of the ratio immediately after bleaching (Fig. 6A for glucose and glutamine) would be consistent with a slight transient buildup of all-trans-retinal (16), perhaps because of a lag in NADPH availability. It should be noted that at early times after bleaching, low amounts of all-trans-retinal have been released, and any standing pool of NADPH makes a comparatively large contribution to the reduction to retinol.…”

Section: Discussionmentioning

confidence: 64%

“…It should be noted that at early times after bleaching, low amounts of all-trans-retinal have been released, and any standing pool of NADPH makes a comparatively large contribution to the reduction to retinol. By 60 min after bleaching, almost all the considerable amount of all-trans-retinal has been released (16), and the conversion of retinal to retinol depends on the generation of NADPH by the metabolic machinery.…”

Section: Discussionmentioning

confidence: 99%

“…By that time, almost all of the retinal has been released from photoactivated rhodopsin (16). Because there is a large amount of retinal released from photoactivated rhodopsin after bleaching and a large fraction of it is present as retinol at any given time (Fig.…”

Section: After Substituting Equation 5 Into Equationmentioning

confidence: 99%

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Mitochondria Contribute to NADPH Generation in Mouse Rod Photoreceptors

Adler

Chen

Koutalos

2014

Journal of Biological Chemistry

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Background:The major source of NADPH is considered to be the pentose phosphate pathway. Results: In isolated mouse rod photoreceptors, blocking metabolite entry into mitochondria substantially reduces NADPH generation. Mitochondrial metabolic substrates support NADPH generation. Conclusion: Mitochondria-linked pathways contribute substantially to NADPH generation in mouse rod photoreceptors. Significance: A wide range of photoreceptor cell functions depend on adequate NADPH supply.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: After Substituting Equation 5 Into Equationmentioning

confidence: 99%

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Mitochondria Contribute to NADPH Generation in Mouse Rod Photoreceptors

Adler

Chen

Koutalos

2014

Journal of Biological Chemistry

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“…One answer may lie in the reduction of the retinal to retinol by retinol dehydrogenase, which pulls the ATR out of the binding reaction. Thus, retinol dehydrogenase proteins may play a key step in preventing futile cyclic ATR binding as has been proposed previously (47,49,61,80,81).…”

Section: Occupancy Of the Cytoplasmic Binding Cleft Of Opsin By Eithementioning

confidence: 67%

Conformational Selection and Equilibrium Governs the Ability of Retinals to Bind Opsin

Schafer¹,

Farrens

2015

Journal of Biological Chemistry

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Background: A current hypothesis proposes that retinal binding to opsin requires transient activation of receptor. Results: Our data show that an active conformation only promotes agonist binding; inverse agonist binding is impaired with increased relative fraction of active receptor. Conclusion: Retinal isomers must match opsin conformation to form a stable complex. Significance: Rhodopsin displays conformational selection for retinal binding similar to other ligand-binding GPCRs.

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Kinetics of Rhodopsin’s Chromophore Monitored in a Single Photoreceptor

Adler

Boyer

Chen

et al. 2015

Methods in Molecular Biology

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Absorption of light isomerizes the retinyl chromophore of the photoreceptor pigment rhodopsin from 11-cis to all-trans, generating the photoactivated rhodopsin form. The photoisomerization of the chromophore however destroys rhodopsin, and its regeneration requires the removal of the all-trans and the supply of fresh 11-cis chromophore. The all-trans chromophore is removed through a series of steps beginning with its release from photoactivated rhodopsin in the form of all-trans-retinal, leaving behind the apoprotein opsin. All-trans-retinal is then reduced to all-trans-retinol, which is transported out of the photoreceptor. Rhodopsin is regenerated from opsin and fresh 11-cis-retinal arriving to the photoreceptor from the retinal pigment epithelium. Both all-trans and 11-cis-retinal can form precursors of lipofuscin, a pigment that accumulates with age in the lysosomal compartment of the retinal pigment epithelium. All-trans-retinal, all-trans-retinol, and lipofuscin precursors all emit significant and distinct fluorescence signals, allowing their monitoring in single photoreceptor cells with fluorescence imaging. Here we describe the procedures for measuring these fluorophores in single mouse rod photoreceptors.

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Rod Outer Segment Retinol Formation Is Independent of Abca4, Arrestin, Rhodopsin Kinase, and Rhodopsin Palmitylation

Abstract: The regeneration of rhodopsin and the recycling of its chromophore are not strongly coupled. Neither the activities of Abca4, rhodopsin kinase, and arrestin, nor the palmitylation of rhodopsin affects the formation of all-trans retinol.

Cited by 19 publications

References 58 publications

Mitochondria Contribute to NADPH Generation in Mouse Rod Photoreceptors

Mitochondria Contribute to NADPH Generation in Mouse Rod Photoreceptors

Conformational Selection and Equilibrium Governs the Ability of Retinals to Bind Opsin

Kinetics of Rhodopsin’s Chromophore Monitored in a Single Photoreceptor

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