Mitochondrial Ca2+ transport in the endothelium: Regulation by ions, redox signalling and mechanical forces

B. Rita Alevriadou, Santhanam Shanmughapriya, Akshar Patel, Peter B. Stathopulos, Muniswamy Madesh

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations

Abstract

Calcium (Ca2+) transport by mitochondria is an important component of the cell Ca2+ homeostasis machinery in metazoans. Ca2+ uptake by mitochondria is a major determinant of bioenergetics and cell fate. Mitochondrial Ca2+ uptake occurs via the mitochondrial Ca2+ uniporter (MCU) complex, an inner mitochondrial membrane protein assembly consisting of the MCU Ca2+ channel, as its core component, and the MCU complex regulatory/auxiliary proteins. In this review, we summarize the current knowledge on the molecular nature of the MCU complex and its regulation by intra-and extramitochondrial levels of divalent ions and reactive oxygen species (ROS). Intracellular Ca2+ concentration ([Ca2+]i), mitochondrial Ca2+ concentration ([Ca2+]m) and mitochondrial ROS (mROS) are intricately coupled in regulating MCU activity. Here, we highlight the contribution of MCU activity to vascular endothelial cell (EC) function. Besides the ionic and oxidant regulation, ECs are continuously exposed to haemodynamic forces (either pulsatile or oscillatory fluid mechanical shear stresses, depending on the precise EC location within the arteries). Thus,we also propose an EC mechanotransduction-mediated regulation of MCU activity in the context of vascular physiology and atherosclerotic vascular disease. & 2017 The Author(s) Published by the Royal Society. All rights reserved.

Original languageEnglish (US)
Article number0672
JournalJournal of the Royal Society Interface
Volume14
Issue number137
DOIs
StatePublished - Dec 1 2017

Keywords

  • Atherosclerosis
  • Mitochondria
  • Mitochondrial Ca uniporter
  • Reactive oxygen species
  • Shear stress
  • Vascular endothelial cell

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering

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