Role of polyhydroxybutyrate in mitochondrial calcium uptake

Matthew Smithen, Pia A. Elustondo, Robert Winkfein, Eleonora Zakharian, Andrey Y. Abramov, Evgeny Pavlov

Research output: Contribution to journalArticle

Abstract

Polyhydroxybutyrate (PHB) is a biological polymer which belongs to the class of polyesters and is ubiquitously present in all living organisms. Mammalian mitochondrial membranes contain PHB consisting of up to 120 hydroxybutyrate residues. Roles played by PHB in mammalian mitochondria remain obscure. It was previously demonstrated that PHB of the size similar to one found in mitochondria mediates calcium transport in lipid bilayer membranes. We hypothesized that the presence of PHB in mitochondrial membrane might play a significant role in mitochondrial calcium transport. To test this, we investigated how the induction of PHB hydrolysis affects mitochondrial calcium transport. Mitochondrial PHB was altered enzymatically by targeted expression of bacterial PHB hydrolyzing enzyme (PhaZ7) in mitochondria of mammalian cultured cells. The expression of PhaZ7 induced changes in mitochondrial metabolism resulting in decreased mitochondrial membrane potential in HepG2 but not in U87 and HeLa cells. Furthermore, it significantly inhibited mitochondrial calcium uptake in intact HepG2, U87 and HeLa cells stimulated by the ATP or by the application of increased concentrations of calcium to the digitonin permeabilized cells. Calcium uptake in PhaZ7 expressing cells was restored by mimicking calcium uniporter properties with natural electrogenic calcium ionophore - ferutinin. We propose that PHB is a previously unrecognized important component of the mitochondrial calcium uptake system.

Original languageEnglish (US)
Pages (from-to)86-94
Number of pages9
JournalCell Calcium
Volume54
Issue number2
DOIs
StatePublished - Aug 2013

Keywords

  • Calcium
  • Inorganic polyphosphate
  • Mitochondria
  • PhaZ7
  • Poly-3-hydroxybutyrate

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Role of polyhydroxybutyrate in mitochondrial calcium uptake'. Together they form a unique fingerprint.

  • Cite this

    Smithen, M., Elustondo, P. A., Winkfein, R., Zakharian, E., Abramov, A. Y., & Pavlov, E. (2013). Role of polyhydroxybutyrate in mitochondrial calcium uptake. Cell Calcium, 54(2), 86-94. https://doi.org/10.1016/j.ceca.2013.04.006