Mitochondria modulate ameloblast Ca2+ signaling

Veronica Costiniti, Guilherme H.S. Bomfim, Maria Neginskaya, Ga Yeon Son, Erna Mitaishvili, Marta Giacomello, Evgeny Pavlov, Rodrigo S Lacruz

Research output: Contribution to journalArticlepeer-review


The role of mitochondria in enamel, the most mineralized tissue in the body, is poorly defined. Enamel is formed by ameloblast cells in two main sequential stages known as secretory and maturation. Defining the physiological features of each stage is essential to understand mineralization. Here, we analyzed functional features of mitochondria in rat primary secretory and maturation-stage ameloblasts focusing on their role in Ca2+ signaling. Quantification of the Ca2+ stored in the mitochondria by trifluoromethoxy carbonylcyanide phenylhydrazone stimulation was comparable in both stages. The release of endoplasmic reticulum Ca2+ pools by adenosine triphosphate in rhod2AM-loaded cells showed similar mitochondrial Ca2+ (mCa2+) uptake. However, mCa2+ extrusion via Na+-Li+-Ca2+ exchanger was more prominent in maturation. To address if mCa2+ uptake via the mitochondrial Ca2+ uniporter (MCU) played a role in cytosolic Ca2+ (cCa2+) buffering, we stimulated Ca2+ influx via the store-operated Ca2+ entry (SOCE) and blocked MCU with the inhibitor Ru265. This inhibitor was first tested using the enamel cell line LS8 cells. Ru265 prevented cCa2+ clearance in permeabilized LS8 cells like ruthenium red, and it did not affect ΔΨm in intact cells. In primary ameloblasts, SOCE stimulation elicited a significantly higher mCa2+ uptake in maturation ameloblasts. The uptake of Ca2+ into the mitochondria was dramatically decreased in the presence of Ru265. Combined, these results suggest an increased mitochondrial Ca2+ handling in maturation but only upon stimulation of Ca2+ influx via SOCE. These functional studies provide insights not only on the role of mitochondria in ameloblast Ca2+ physiology, but also advance the concept that SOCE and mCa2+ uptake are complementary processes in biological mineralization.

Original languageEnglish (US)
Article numbere22169
JournalFASEB Journal
Issue number2
StatePublished - Feb 2022


  • Adenosine Triphosphate/metabolism
  • Ameloblasts/metabolism
  • Animals
  • Calcium/metabolism
  • Calcium Channels/metabolism
  • Calcium Signaling/physiology
  • Cells, Cultured
  • Cytosol/metabolism
  • Endoplasmic Reticulum/metabolism
  • Mitochondria/metabolism
  • Rats
  • Rats, Sprague-Dawley

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry
  • Biotechnology


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