Regulation of mitochondrial fission by intracellular Ca2+ in rat ventricular myocytes

Jennifer Hom, Tianzheng Yu, Yisang Yoon, George Porter, Shey Shing Sheu

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Mitochondria are dynamic organelles that constantly undergo fission, fusion, and movement. Increasing evidence indicates that these dynamic changes are intricately related to mitochondrial function, suggesting that mitochondrial form and function are linked. Calcium (Ca2+) is one signal that has been shown to both regulate mitochondrial fission in various cell types and stimulate mitochondrial enzymes involved in ATP generation. However, although Ca2+ plays an important role in adult cardiac muscle cells for excitation-metabolism coupling, little is known about whether Ca2+ can regulate their mitochondrial morphology. Therefore, we tested the role of Ca2+ in regulating cardiac mitochondrial fission. We found that neonatal and adult cardiomyocyte mitochondria undergo rapid and transient fragmentation upon a thapsigargin (TG)- or KCl-induced cytosolic Ca2+ increase. The mitochondrial fission protein, DLP1, participates in this mitochondrial fragmentation, suggesting that cardiac mitochondrial fission machinery may be regulated by intracellular Ca2+ signaling. Moreover, the TG-induced fragmentation was also associated with an increase in reactive oxygen species (ROS) formation, suggesting that activation of mitochondrial fission machinery is an early event for Ca2+-mediated ROS generation in cardiac myocytes. These results suggest that Ca2+, an important regulator of muscle contraction and energy generation, also dynamically regulates mitochondrial morphology and ROS generation in cardiac myocytes.

Original languageEnglish (US)
Pages (from-to)913-921
Number of pages9
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number6-7
DOIs
StatePublished - Jun 2010

Keywords

  • Calcium
  • Cardiac muscle
  • Mitochondria
  • Mitochondrial fusion and fission
  • Reactive oxygen species
  • Ventricular myocytes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Regulation of mitochondrial fission by intracellular Ca<sup>2+</sup> in rat ventricular myocytes'. Together they form a unique fingerprint.

  • Cite this