Mitochondrial VDAC, the Na+/Ca2+ exchanger, and the Ca2+ uniporter in Ca2+ dynamics and signaling

Varda Shoshan-Barmatz, Soumasree De

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

25 Scopus citations

Abstract

Mitochondrial Ca2+ uptake and release play pivotal roles in cellular physiology by regulating intracellular Ca2+ signaling, energy metabolism, and cell death. Ca2+ transport across the inner and outer mitochondrial membranes (IMM, OMM, respectively), is mediated by several proteins, including the voltage-dependent anion channel 1 (VDAC1) in the OMM, and the mitochondrial Ca2+ uniporter (MCU) and Na+-dependent mitochondrial Ca2+ efflux transporter, (the NCLX), both in the IMM. By transporting Ca2+ across the OMM to the mitochondrial inner-membrane space (IMS), VDAC1 allows Ca2+ access to the MCU, facilitating transport of Ca2+ to the matrix, and also from the IMS to the cytosol. Intra-mitochondrial Ca2+ controls energy production and metabolism by modulating critical enzymes in the tricarboxylic acid (TCA) cycle and fatty acid oxidation. Thus, by transporting Ca2+, VDAC1 plays a fundamental role in regulating mitochondrial Ca2+ homeostasis, oxidative phosphorylation, and Ca2+ crosstalk among mitochondria, cytoplasm, and the endoplasmic reticulum (ER). VDAC1 has also been recognized as a key protein in mitochondria-mediated apoptosis, and apoptosis stimuli induce overexpression of the protein in a Ca2+-dependent manner. The overexpressed VDAC1 undergoes oligomerization leading to the formation of a channel, through which apoptogenic agents can be released. Here, we review the roles of VDAC1 in mitochondrial Ca2+ homeostasis, in apoptosis, and in diseases associated with mitochondria dysfunction.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages323-347
Number of pages25
DOIs
StatePublished - 1 Jan 2017

Publication series

NameAdvances in Experimental Medicine and Biology
Volume981
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Ca homeostasis
  • Ca transport
  • ER-mitochondria crosstalk
  • MCU
  • Mitochondria
  • NCLX
  • VDAC

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

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