Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas

Anne Hong-Hermesdorf, Marcus Miethke, Sean D. Gallaher, Janette Kropat, Sheel C. Dodani, Jefferson Chan, Dulmini Barupala, Dylan W. Domaille, Dyna I. Shirasaki, Joseph A. Loo, Peter K. Weber, Jennifer Pett-Ridge, Timothy L. Stemmler, Christopher J. Chang, Sabeeha S. Merchant

Research output: Contribution to journalArticlepeer-review


We identified a Cu-accumulating structure with a dynamic role in intracellular Cu homeostasis. During Zn limitation, Chlamydomonas reinhardtii hyperaccumulates Cu, a process dependent on the nutritional Cu sensor CRR1, but it is functionally Cu deficient. Visualization of intracellular Cu revealed major Cu accumulation sites coincident with electron-dense structures that stained positive for low pH and polyphosphate, suggesting that they are lysosome-related organelles. Nano-secondary ion MS showed colocalization of Ca and Cu, and X-ray absorption spectroscopy was consistent with Cu(+) accumulation in an ordered structure. Zn resupply restored Cu homeostasis concomitant with reduced abundance of these structures. Cu isotope labeling demonstrated that sequestered Cu(+) became bioavailable for the synthesis of plastocyanin, and transcriptome profiling indicated that mobilized Cu became visible to CRR1. Cu trafficking to intracellular accumulation sites may be a strategy for preventing protein mismetallation during Zn deficiency and enabling efficient cuproprotein metallation or remetallation upon Zn resupply.

Original languageEnglish (US)
Pages (from-to)1034-1042
Number of pages9
JournalNature chemical biology
Issue number12
StatePublished - Dec 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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