Inhibitors of the mitochondrial calcium uniporter for the treatment of disease

Curr Opin Chem Biol. 2020 Apr:55:9-18. doi: 10.1016/j.cbpa.2019.11.006. Epub 2019 Dec 20.

Abstract

The mitochondrial calcium uniporter (MCU) is a protein located in the inner mitochondrial membrane that is responsible for mitochondrial Ca2+ uptake. Under certain pathological conditions, dysregulation of Ca2+ uptake through the MCU results in cellular dysfunction and apoptotic cell death. Given the role of the MCU in human disease, researchers have developed compounds capable of inhibiting mitochondrial calcium uptake as tools for understanding the role of this protein in cell death. In this article, we describe recent findings on the role of the MCU in mediating pathological conditions and the search for small-molecule inhibitors of this protein for potential therapeutic applications.

Keywords: Biological calcium trafficking; Mitochondrial calcium uniporter; Mitochondrial disease; Ruthenium coordination compounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Calcium Channels / metabolism*
  • Calcium Signaling / drug effects
  • Cell Membrane Permeability
  • Humans
  • Ischemia / drug therapy
  • Ischemic Stroke / drug therapy
  • Metals / chemistry*
  • Metals / metabolism
  • Metals / pharmacology
  • Mitochondria / metabolism
  • Neoplasms / drug therapy
  • Organic Chemicals / chemistry*
  • Organic Chemicals / metabolism
  • Organic Chemicals / pharmacology
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology
  • Protein Multimerization
  • Reperfusion Injury / drug therapy

Substances

  • Calcium Channels
  • Metals
  • Organic Chemicals
  • Organometallic Compounds
  • mitochondrial calcium uniporter