Mitochondrial calcium uniporter complex modulation in cancerogenesis

Cell Cycle. 2019 May;18(10):1068-1083. doi: 10.1080/15384101.2019.1612698. Epub 2019 May 10.

Abstract

Aberrations in mitochondrial Ca2+ homeostasis have been associated with different pathological conditions, including neurological defects, cardiovascular diseases, and, in the last years, cancer. With the recent molecular identification of the mitochondrial calcium uniporter (MCU) complex, the channel that allows Ca2+ accumulation into the mitochondrial matrix, alterations in the expression levels or functioning in one or more MCU complex members have been linked to different cancers and cancer-related phenotypes. In this review, we will analyze the role of the uniporter and mitochondrial Ca2+ derangements in modulating cancer cell sensitivity to death, invasiveness, and migratory capacity, as well as cancer progression in vivo. We will also discuss some critical points and contradictory results to highlight the consequence of MCU complex modulation in tumor development.

Keywords: Mitochondria; Mitochondrial Calcium Uniporter (MCU); calcium; cancer.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / chemistry
  • Calcium Channels / metabolism
  • Calcium Channels / physiology*
  • Carcinogenesis / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Homeostasis
  • Humans
  • Mitochondria / metabolism*
  • Models, Biological

Substances

  • Calcium Channels
  • mitochondrial calcium uniporter
  • Calcium

Grants and funding

This work was supported by the Associazione Italiana per la Ricerca sul Cancro [IG‐18624]; Associazione Italiana per la Ricerca sul Cancro [IG19803]; Fondazione Telethon [GGP15219/B]; Fondazione Umberto Veronesi; Ministero della Salute [GR-2016-02364602]; Ministero dell’Istruzione, dell’Università e della Ricerca [2017E5L5P3]; Ministero dell’Istruzione, dell’Università e della Ricerca [20177E9EPY].