Downregulation of ATP Synthase Subunit-6, Cytochrome<i>c</i>Oxidase-III, and NADH Dehydrogenase-3 by Bright Cyclic Light in the Rat Retina

Hu, Huang; Li, Feng; Alvarez, Richard A.; Ash, John D.; Anderson, Robert E.

doi:10.1167/iovs.03-1081

Cited by 27 publications

(20 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such altered expression 30 and regulation of mitochondrial ATP synthase genes in response to pH changes or other signals are well-documented. 31,32 Huang et al 33 have recently reported down regulation of ATP synthase subunit 6 and other mitochondrial genes in the retinas of rats in response to bright cyclic light.…”

Section: Discussionmentioning

confidence: 98%

Differential gene expression during apoptosis induced by a serum factor: Role of mitochondrial F0-F1 ATP synthase complex

Singh

Khar

2005

Apoptosis

View full text Add to dashboard Cite

The number of genes that are up regulated or down regulated during apoptosis is large and still increasing. In an attempt to characterize differential gene expression during serum factor induced apoptosis in AK-5 cells (a rat histiocytoma), we found subunit 6 and subunit 8 of the transmembrane proton channel and subunit alpha of the catalytic core of the mitochondrial F(0)-F(1) ATP synthase complex to be up regulated during apoptosis. The increase in the expression levels of these subunits was concomitant with a transient increase in the intracellular ATP levels, suggesting that the increase in cellular ATP content is a result of the increase in the expression of ATP synthase subunits' gene and de novo protein synthesis. Depleting the cellular ATP levels with oligomycin inhibited apoptosis significantly, pointing to the requirement of ATP during apoptosis. Caspase 1 and caspase 3 activity and the loss of mitochondrial membrane potential were also inhibited by oligomycin during apoptosis in these cells, suggesting that the oligomycin induced inhibition of apoptosis could be due to inhibition of caspase activity and inhibition of mitochondrial depolarization. However, cytochrome C release during apoptosis was found to be completely independent of intracellular ATP content. Besides the ATP synthase complex genes, other mitochondrial genes like cytochrome C oxidase subunit II and III also showed elevated levels of expression during apoptosis. This kind of a mitochondrial gene expression profile suggests that in AK-5 cells, these genes are upregulated in a time-linked manner to ensure sufficient intracellular ATP levels and an efficient functioning of the mitochondrial respiratory chain for successful completion of the apoptotic pathway.

show abstract

Section: Discussionmentioning

confidence: 98%

Differential gene expression during apoptosis induced by a serum factor: Role of mitochondrial F0-F1 ATP synthase complex

Singh

Khar

2005

Apoptosis

View full text Add to dashboard Cite

show abstract

“…In subsequent studies, Penn and Anderson and associates reported that light history also affected retinal antioxidant levels, ROS lipid composition and light damage susceptibility (Penn et al , 1987; Penn and Anderson, 1987). More recently, long term bright light conditioning has been shown to alter the expression of mitochondrial enzymes (Huang et al , 2004) and to protect against retinal light damage by decreasing DHA levels (Li et al , 2001). Short term preconditioning with bright light also leads to protection against retinal damage by subsequent intense light treatment (Liu et al , 1998).…”

Section: Factors Involved In the Light Damage Processmentioning

confidence: 99%

Retinal light damage: Mechanisms and protection

Organisciak

Vaughan

2010

Progress in Retinal and Eye Research

481

394

View full text Add to dashboard Cite

By its action on rhodopsin, light triggers the well-known visual transduction cascade, but can also induce cell damage and death through phototoxic mechanisms --a comprehensive understanding of which is still elusive despite more than 40 years of research. Herein, we integrate recent experimental findings to address several hypotheses of retinal light damage, premised in part on the close anatomical and metabolic relationships between the photoreceptors and the retinal pigment epithelium. We begin by reviewing the salient features of light damage, recently joined by evidence for retinal remodeling which has implications for the prognosis of recovery of function in retinal degenerations. We then consider select factors that influence the progression of the damage process and the extent of visual cell loss. Traditional, genetically-modified, and emerging animal models are discussed, with particular emphasis on cone visual cells. Exogenous and endogenous retinal protective factors are explored, with implications for light damage mechanisms and some suggested avenues for future research. Synergies are known to exist between our long term light environment and photoreceptor cell death in retinal disease. Understanding the molecular mechanisms of light damage in a variety of animal models can provide valuable insights into the effects of light in clinical disorders and may form the basis of future therapies to prevent or delay visual cell loss.

show abstract

“…On the other hand, mitochondria will have to produce more ATP to sustain photoreceptor activities. As a result, the mitochondrial enzymes that are responsible for ATP production should be more activated in darkness, which is supported by Huang et al (2004) where the mitochondrial enzymes cytochrome C oxidase III and adenosine triphosphatase-6 are downregulated by higher light intensity. Thus, the overall ATP production may be lower in the presence of bright light.…”

Section: Discussionmentioning

confidence: 91%

A new role for AMP‐activated protein kinase in the circadian regulation of L‐type voltage‐gated calcium channels in late‐stage embryonic retinal photoreceptors

Huang

Shi

Lin

et al. 2015

Journal of Neurochemistry

View full text Add to dashboard Cite

AMPK is a cellular energy sensor, which is activated when the intracellular ATP production decreases. The activities of AMPK display circadian rhythms in various organs and tissues, indicating that AMPK is involved in the circadian regulation of cellular metabolism. In vertebrate retina, the circadian clocks regulate many aspects of retinal function and physiology, including light/dark adaption, but whether and how AMPK was involved in the retinal circadian rhythm was not known. We hypothesized that the activation of AMPK (measured as phosphorylated AMPK) in the retina was under circadian control, and AMPK might interact with other intracellular signaling molecules to regulate photoreceptor physiology. We combined ATP assays, Western blots, immunostaining, patch-clamp recordings, and pharmacological treatments to decipher the role of AMPK in the circadian regulation of photoreceptor physiology. We found that the overall retinal ATP content displayed a diurnal rhythm that peaked at early night, which was nearly anti-phase to the diurnal and circadian rhythms of AMPK phosphorylation. AMPK was also involved in the circadian phase-dependent regulation of photoreceptor L-type voltage-gated calcium channels (L-VGCCs), the ion channel essential for sustained neurotransmitter release. The activation of AMPK dampened the L-VGCC currents at night with a corresponding decrease in protein expression of the L-VGCCα1 pore-forming subunit, while inhibition of AMPK increased the L-VGCC current during the day. AMPK appeared to be upstream of extracellular-signal-regulated kinase (ERK) and mammalian/mechanistic target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Hence, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology. We found that in chicken embryonic retina, the activation of AMP-Activated Protein Kinase (AMPK) is under circadian control and anti-phase to the retinal ATP rhythm. While ATP content is higher at night, phosphorylated AMPK (pAMPK) is higher during the day. AMPK appears to be upstream of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and mammalian target of rapamycin complex 1 (mTORC1) but downstream of adenylyl cyclase in regulating the circadian rhythm of L-VGCCs. Therefore, as a cellular energy sensor, AMPK integrates into the cell signaling network to regulate the circadian rhythm of photoreceptor physiology.

show abstract

Downregulation of ATP Synthase Subunit-6, CytochromecOxidase-III, and NADH Dehydrogenase-3 by Bright Cyclic Light in the Rat Retina

Cited by 27 publications

References 37 publications

Differential gene expression during apoptosis induced by a serum factor: Role of mitochondrial F0-F1 ATP synthase complex

Differential gene expression during apoptosis induced by a serum factor: Role of mitochondrial F0-F1 ATP synthase complex

Retinal light damage: Mechanisms and protection

A new role for AMP‐activated protein kinase in the circadian regulation of L‐type voltage‐gated calcium channels in late‐stage embryonic retinal photoreceptors

Contact Info

Product

Resources

About