Complex I and II are required for normal mitochondrial Ca2+ homeostasis

Mitochondrion. 2019 Nov:49:73-82. doi: 10.1016/j.mito.2019.07.004. Epub 2019 Jul 13.

Abstract

Cytosolic calcium (cCa2+) entry into mitochondria is facilitated by the mitochondrial membrane potential (ΔΨm), an electrochemical gradient generated by the electron transport chain (ETC). Is has been assumed that as long as mutations that affect the ETC do not affect the ΔΨm, the mitochondrial Ca2+ (mCa2+) homeostasis remains normal. We show that knockdown of NDUFAF3 and SDHB reduce ETC activity altering mCa2+ efflux and influx rates while ΔΨm remains intact. Shifting the equilibrium toward lower [Ca2+]m accumulation renders cells resistant to death. Our findings reveal an unexpected relationship between complex I and II with the mCa2+ homeostasis independent of ΔΨm.

Keywords: Calcium flux; Cell death; Migration; Mitochondrial membrane potential.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Homeostasis*
  • Humans
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / genetics
  • Mitochondria / enzymology*
  • Mitochondria / genetics
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism*

Substances

  • Mitochondrial Proteins
  • NDUFAF3 protein, human
  • SDHB protein, human
  • Succinate Dehydrogenase
  • Electron Transport Complex I
  • Calcium