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Title: Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease

Abstract

Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases. Here we combine metal imaging and optical imaging techniques at a variety of spatial resolutions to identify tissues and structures with altered copper levels in the Calamitygw71 zebrafish model of Menkes disease. Rapid profiling of tissue slices with LA-ICP-MS identified reduced copper levels in the brain, neuroretina, and liver of Menkes fish compared to control specimens. High resolution nanoSIMS imaging of the neuroretina, combined with electron and confocal microscopies, identified the megamitochondria of photoreceptors as loci of copper accumulation in wildtype fish, with lower levels of megamitochondrial copper observed in Calamitygw71 zebrafish. Interestingly, this localized copper decrease does not result in impaired photoreceptor development or altered megamitochondrial morphology, suggesting the prioritization of copper at sufficient levels for maintaining essential mitochondrialmore » functions. Together, these data establish the Calamitygw71 zebrafish as an optically transparent in vivo model for the study of neural copper misregulation, illuminate a role for the ATP7A copper exporter in trafficking copper to the neuroretina, and highlight the utility of combining multiple imaging techniques for studying metals in whole organism settings with spatial resolution.« less

Authors:
 [1];  [2];  [1];  [1];  [1];  [1];  [2];  [3]
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  1. Univ. of California, Berkeley, CA (United States)
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Univ. of California, Berkeley, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); Fannie and John Hertz Foundation; Canadian Inst. for Advanced Research (CIFAR); USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1467817
Alternate Identifier(s):
OSTI ID: 1434089; OSTI ID: 1532304
Report Number(s):
LLNL-JRNL-745593
Journal ID: ISSN 1756-5901; METAIR; 930110
Grant/Contract Number:  
AC52-07NA27344; GM 79465; T32 GM066698; SCW1039; AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Metallomics
Additional Journal Information:
Journal Volume: 10; Journal Issue: 3; Journal ID: ISSN 1756-5901
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Ackerman, Cheri M., Weber, Peter K., Xiao, Tong, Thai, Bao, Kuo, Tiffani J., Zhang, Emily, Pett-Ridge, Jennifer, and Chang, Christopher J. Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease. United States: N. p., 2018. Web. doi:10.1039/c7mt00349h.
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Ackerman, Cheri M., Weber, Peter K., Xiao, Tong, Thai, Bao, Kuo, Tiffani J., Zhang, Emily, Pett-Ridge, Jennifer, & Chang, Christopher J. Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease. United States. https://doi.org/10.1039/c7mt00349h
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Ackerman, Cheri M., Weber, Peter K., Xiao, Tong, Thai, Bao, Kuo, Tiffani J., Zhang, Emily, Pett-Ridge, Jennifer, and Chang, Christopher J. Tue . "Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease". United States. https://doi.org/10.1039/c7mt00349h. https://www.osti.gov/servlets/purl/1467817.
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@article{osti_1467817,
title = {Multimodal LA-ICP-MS and nanoSIMS imaging enables copper mapping within photoreceptor megamitochondria in a zebrafish model of Menkes disease},
author = {Ackerman, Cheri M. and Weber, Peter K. and Xiao, Tong and Thai, Bao and Kuo, Tiffani J. and Zhang, Emily and Pett-Ridge, Jennifer and Chang, Christopher J.},
abstractNote = {Copper is essential for eukaryotic life, and animals must acquire this nutrient through the diet and distribute it to cells and organelles for proper function of biological targets. Indeed, mutations in the central copper exporter ATP7A contribute to a spectrum of diseases, including Menkes disease, with symptoms ranging from neurodegeneration to lax connective tissue. As such, a better understanding of the fundamental impacts of ATP7A mutations on in vivo copper distributions is of relevance to those affected by these diseases. Here we combine metal imaging and optical imaging techniques at a variety of spatial resolutions to identify tissues and structures with altered copper levels in the Calamitygw71 zebrafish model of Menkes disease. Rapid profiling of tissue slices with LA-ICP-MS identified reduced copper levels in the brain, neuroretina, and liver of Menkes fish compared to control specimens. High resolution nanoSIMS imaging of the neuroretina, combined with electron and confocal microscopies, identified the megamitochondria of photoreceptors as loci of copper accumulation in wildtype fish, with lower levels of megamitochondrial copper observed in Calamitygw71 zebrafish. Interestingly, this localized copper decrease does not result in impaired photoreceptor development or altered megamitochondrial morphology, suggesting the prioritization of copper at sufficient levels for maintaining essential mitochondrial functions. Together, these data establish the Calamitygw71 zebrafish as an optically transparent in vivo model for the study of neural copper misregulation, illuminate a role for the ATP7A copper exporter in trafficking copper to the neuroretina, and highlight the utility of combining multiple imaging techniques for studying metals in whole organism settings with spatial resolution.},
doi = {10.1039/c7mt00349h},
journal = {Metallomics},
number = 3,
volume = 10,
place = {United States},
year = {Tue Mar 06 00:00:00 EST 2018},
month = {Tue Mar 06 00:00:00 EST 2018}
}
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https://doi.org/10.1039/c7mt00349h
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Works referenced in this record:

How copper traverses cellular membranes through the mammalian copper transporter 1, Ctr1: Mammalian copper uptake and mobilization by Ctr1
journal, February 2014

  • Öhrvik, Helena; Thiele, Dennis J.
  • Annals of the New York Academy of Sciences, Vol. 1314, Issue 1
  • DOI: 10.1111/nyas.12371

Copper dyshomoeostasis in Parkinson's disease: implications for pathogenesis and indications for novel therapeutics
journal, March 2016

  • Davies, Katherine M.; Mercer, Julian F. B.; Chen, Nicholas
  • Clinical Science, Vol. 130, Issue 8
  • DOI: 10.1042/cs20150153

Biochemical basis of regulation of human copper-transporting ATPases
journal, July 2007

  • Lutsenko, Svetlana; LeShane, Erik S.; Shinde, Ujwal
  • Archives of Biochemistry and Biophysics, Vol. 463, Issue 2
  • DOI: 10.1016/j.abb.2007.04.013

Dynamic organization of mitochondria in human heart and in myocardial disease
journal, October 2009

  • Hoppel, Charles L.; Tandler, Bernard; Fujioka, Hisashi
  • The International Journal of Biochemistry & Cell Biology, Vol. 41, Issue 10
  • DOI: 10.1016/j.biocel.2009.05.004

The ciliopathy gene cc2d2a controls zebrafish photoreceptor outer segment development through a role in Rab8-dependent vesicle trafficking
journal, August 2011

  • Bachmann-Gagescu, Ruxandra; Phelps, Ian G.; Stearns, George
  • Human Molecular Genetics, Vol. 20, Issue 20
  • DOI: 10.1093/hmg/ddr332

Megamitochondria in the serous acinar cells of the submandibular gland of the neotropical fruit bat,Artibeus obscurus
journal, May 1997

Protocol for production of matrix-matched brain tissue standards for imaging by laser ablation-inductively coupled plasma-mass spectrometry
journal, January 2013

  • Hare, Dominic J.; Lear, Jessica; Bishop, David
  • Analytical Methods, Vol. 5, Issue 8
  • DOI: 10.1039/c3ay26248k

Photoreceptor inner segments in monkey and human retina: Mitochondrial density, optics, and regional variation
journal, July 2002

Chemical alterations to murine brain tissue induced by formalin fixation: implications for biospectroscopic imaging and mapping studies of disease pathogenesis
journal, January 2011

  • Hackett, Mark J.; McQuillan, James A.; El-Assaad, Fatima
  • The Analyst, Vol. 136, Issue 14
  • DOI: 10.1039/c0an00269k

Human copper transporters: mechanism, role in human diseases and therapeutic potential
journal, September 2009

  • Gupta, Arnab; Lutsenko, Svetlana
  • Future Medicinal Chemistry, Vol. 1, Issue 6
  • DOI: 10.4155/fmc.09.84

Independent component analysis for biomedical signals
journal, December 2004

The many “faces” of copper in medicine and treatment
journal, April 2014

Cornea, retina, and lens morphology in five Soricidae species (Soricomorpha: Mammalia)
journal, April 2009

  • Lluch, Sara; López-Fuster, María José; Ventura, Jacint
  • Anatomical Science International, Vol. 84, Issue 4
  • DOI: 10.1007/s12565-009-0042-1

Giant mitochondria distinct from enlarged mitochondria in secretory and ciliated cells of gerbil trachea and bronchioles
journal, July 1990

  • Spicer, S. S.; Parmley, R. T.; Boyd, L.
  • American Journal of Anatomy, Vol. 188, Issue 3
  • DOI: 10.1002/aja.1001880306

Histochemical localization of copper in various organs of brindled mice after copper therapy
journal, January 1995

The locations of mitochondria in mammalian photoreceptors: Relation to retinal vasculature
journal, January 2008

φXANES: In vivo imaging of metal-protein coordination environments
journal, February 2016

  • James, Simon A.; Hare, Dominic J.; Jenkins, Nicole L.
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep20350

Copper mediated neurological disorder: Visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease
journal, January 2015

  • Ahuja, Anami; Dev, Kapil; Tanwar, Ranjeet S.
  • Journal of Trace Elements in Medicine and Biology, Vol. 29
  • DOI: 10.1016/j.jtemb.2014.05.003

Mottled Mice and Non-Mammalian Models of Menkes Disease
journal, December 2015

  • Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł
  • Frontiers in Molecular Neuroscience, Vol. 8
  • DOI: 10.3389/fnmol.2015.00072

Flow of energy in the outer retina in darkness and in light
journal, May 2010

  • Linton, J. D.; Holzhausen, L. C.; Babai, N.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 19
  • DOI: 10.1073/pnas.1002471107

A Targetable Fluorescent Sensor Reveals That Copper-Deficient SCO1 and SCO2 Patient Cells Prioritize Mitochondrial Copper Homeostasis
journal, June 2011

  • Dodani, Sheel C.; Leary, Scot C.; Cobine, Paul A.
  • Journal of the American Chemical Society, Vol. 133, Issue 22
  • DOI: 10.1021/ja2004158

The Role of Copper in Neurodegenerative Disease
journal, August 1999

  • Waggoner, Darrel J.; Bartnikas, Thomas B.; Gitlin, Jonathan D.
  • Neurobiology of Disease, Vol. 6, Issue 4
  • DOI: 10.1006/nbdi.1999.0250

Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas
journal, October 2014

  • Hong-Hermesdorf, Anne; Miethke, Marcus; Gallaher, Sean D.
  • Nature Chemical Biology, Vol. 10, Issue 12
  • DOI: 10.1038/nchembio.1662

Giant mitochondria in the retina cone inner segments of shrews of genus Sorex (Insectivora, Soricidae) : Giant Mitochondria in
journal, April 2003

  • Lluch, Sara; López-Fuster, María José; Ventura, Jacint
  • The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, Vol. 272A, Issue 2
  • DOI: 10.1002/ar.a.10066

Yeast Contain a Non-proteinaceous Pool of Copper in the Mitochondrial Matrix
journal, January 2004

  • Cobine, Paul A.; Ojeda, Luis D.; Rigby, Kevin M.
  • Journal of Biological Chemistry, Vol. 279, Issue 14
  • DOI: 10.1074/jbc.M312693200

Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity
journal, January 2016

  • Kumar, Dhivya; Blaby-Haas, Crysten E.; Merchant, Sabeeha S.
  • Journal of Cell Science, Vol. 129, Issue 5
  • DOI: 10.1242/jcs.177410

Analytical Methods for Imaging Metals in Biology: From Transition Metal Metabolism to Transition Metal Signaling
journal, December 2016

Translational research investigations on ATP7A: an important human copper ATPase: Translational research investigations on ATP7A
journal, April 2014

  • Kaler, Stephen G.
  • Annals of the New York Academy of Sciences, Vol. 1314, Issue 1
  • DOI: 10.1111/nyas.12422

ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones
journal, March 2016

  • Masuda, Takamasa; Wada, Yasutaka; Kawamura, Satoru
  • Scientific Reports, Vol. 6, Issue 1
  • DOI: 10.1038/srep22360

Morphogenesis of megamitochondria in the retinal cone inner segments of Tupaia belangeri (Scandentia)
journal, June 1996

  • Knabe, Wolfgang; Kuhn, Hans-Jürg
  • Cell and Tissue Research, Vol. 285, Issue 1
  • DOI: 10.1007/s004410050614

The mitochondrion: a central architect of copper homeostasis
journal, January 2017

  • Baker, Zakery N.; Cobine, Paul A.; Leary, Scot C.
  • Metallomics, Vol. 9, Issue 11
  • DOI: 10.1039/c7mt00221a

Biotagging of Specific Cell Populations in Zebrafish Reveals Gene Regulatory Logic Encoded in the Nuclear Transcriptome
journal, April 2017

Transgenic Zebrafish Expressing mCherry in the Mitochondria of Dopaminergic Neurons
journal, October 2015

  • Noble, Sandra; Godoy, Rafael; Affaticati, Pierre
  • Zebrafish, Vol. 12, Issue 5
  • DOI: 10.1089/zeb.2015.1085

Modifying factors and phenotypic diversity in Wilson's disease: Modifying factors in Wilson's disease
journal, April 2014

  • Lutsenko, Svetlana
  • Annals of the New York Academy of Sciences, Vol. 1315, Issue 1
  • DOI: 10.1111/nyas.12420

“Lens Mitochondria” in the Retinal Cones of the Tree-shrew Tupaia belangeri
journal, February 1997

Reduced Zinc and Copper in the Retinal Pigment Epithelium and Choroid in Age-related Macular Degeneration
journal, February 2009

  • Erie, Jay C.; Good, Jonathan A.; Butz, John A.
  • American Journal of Ophthalmology, Vol. 147, Issue 2
  • DOI: 10.1016/j.ajo.2008.08.014

Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development
journal, June 2001

  • Lee, J.; Prohaska, J. R.; Thiele, D. J.
  • Proceedings of the National Academy of Sciences, Vol. 98, Issue 12
  • DOI: 10.1073/pnas.111058698

Update on the clinical management of Wilson's disease
journal, January 2017

Bioinorganic Life and Neural Activity: Toward a Chemistry of Consciousness?
journal, March 2017

Oxygen Distribution and Consumption within the Retina in Vascularised and Avascular Retinas and in Animal Models of Retinal Disease
journal, March 2001

Menkes disease: what a multidisciplinary approach can do
journal, January 2016

  • Prasad, Asuri Narayan; Ojha, Rahul
  • Journal of Multidisciplinary Healthcare, Vol. Volume 9
  • DOI: 10.2147/jmdh.s93454

An Overview and Update of ATP7A Mutations Leading to Menkes Disease and Occipital Horn Syndrome
journal, March 2013

Methylmalonic acidemia: A megamitochondrial disorder affecting the kidney
journal, May 2014

  • Zsengellér, Zsuzsanna K.; Aljinovic, Nika; Teot, Lisa A.
  • Pediatric Nephrology, Vol. 29, Issue 11
  • DOI: 10.1007/s00467-014-2847-y

Nano-scale secondary ion mass spectrometry — A new analytical tool in biogeochemistry and soil ecology: A review article
journal, August 2007

Quantification of Oxygen Consumption in Retina Ex Vivo Demonstrates Limited Reserve Capacity of Photoreceptor Mitochondria
journal, December 2015

  • Kooragayala, Keshav; Gotoh, Norimoto; Cogliati, Tiziana
  • Investigative Opthalmology & Visual Science, Vol. 56, Issue 13
  • DOI: 10.1167/iovs.15-17901

Characterization of the Signal That Directs Tom20 to the Mitochondrial Outer Membrane
journal, October 2000

  • Kanaji, Sachiko; Iwahashi, Jun; Kida, Yuichiro
  • The Journal of Cell Biology, Vol. 151, Issue 2
  • DOI: 10.1083/jcb.151.2.277

Affinity gradients drive copper to cellular destinations
journal, May 2010

  • Banci, Lucia; Bertini, Ivano; Ciofi-Baffoni, Simone
  • Nature, Vol. 465, Issue 7298
  • DOI: 10.1038/nature09018

Menkes disease New ocular and electroretinographic findings
journal, June 1998

ATP7A-related copper transport diseases—emerging concepts and future trends
journal, January 2011

Real-time imaging of mitochondria in transgenic zebrafish expressing mitochondrially targeted GFP
journal, September 2008

  • Jung Kim, Min; Ho Kang, Kyung; Kim, Cheol-Hee
  • BioTechniques, Vol. 45, Issue 3
  • DOI: 10.2144/000112909

Imaging and 3D Elemental Characterization of Intact Bacterial Spores by High-Resolution Secondary Ion Mass Spectrometry
journal, August 2008

  • Ghosal, Sutapa; Fallon, Stewart J.; Leighton, Terrance J.
  • Analytical Chemistry, Vol. 80, Issue 15
  • DOI: 10.1021/ac8006279

Visual pathway abnormalities Wilson’s disease
journal, May 2000

Copper-transporting ATPases ATP7A and ATP7B: cousins, not twins
journal, November 2007

  • Linz, Rachel; Lutsenko, Svetlana
  • Journal of Bioenergetics and Biomembranes, Vol. 39, Issue 5-6
  • DOI: 10.1007/s10863-007-9101-2

Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress
journal, July 2015

The Ocular Pathology of Menkes' Disease: (Kinky Hair Disease)
journal, December 1968

Variability in mitochondria of zebrafish photoreceptor ellipsoids
journal, January 2014

The Presence of Megamitochondria in the Ellipsoid of Photoreceptor Inner Segment of the Zebrafish Retina
journal, December 2005

  • Kim, J.; Lee, E.; Chang, B. S.
  • Anatomia, Histologia, Embryologia: Journal of Veterinary Medicine Series C, Vol. 34, Issue 6
  • DOI: 10.1111/j.1439-0264.2005.00612.x

Copper trafficking to the secretory pathway
journal, January 2016

Atp7a determines a hierarchy of copper metabolism essential for notochord development
journal, August 2006

Megamitochondria formation - physiology and pathology
journal, October 2002

Retinal Localization and Copper-Dependent Relocalization of the Wilson and Menkes Disease Proteins
journal, July 2006

  • Krajacic, Predrag; Qian, Ying; Hahn, Paul
  • Investigative Opthalmology & Visual Science, Vol. 47, Issue 7
  • DOI: 10.1167/iovs.05-1601

Copper is an endogenous modulator of neural circuit spontaneous activity
journal, November 2014

  • Dodani, Sheel C.; Firl, Alana; Chan, Jefferson
  • Proceedings of the National Academy of Sciences, Vol. 111, Issue 46
  • DOI: 10.1073/pnas.1409796111

NASH and cryptogenic cirrhosis: A histological analysis
journal, October 2009

Correction: Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress
journal, March 2018

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