Cancer cells with defective oxidative phosphorylation require endoplasmic reticulum-to-mitochondria Ca²⁺ transfer for survival.

ABSTRACT: Spontaneous Ca²⁺ signaling from the InsP₃R intracellular Ca²⁺ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic precursors. To investigate the role of mitochondrial Ca²⁺ uptake in regulating bioenergetics in these cells, we used OXPHOS-competent and OXPHOS-defective cells. Inhibition of InsP₃R activity or mitochondrial Ca²⁺ uptake increased α-ketoglutarate (αKG) abundance and the NAD⁺/NADH ratio, indicating that constitutive endoplasmic reticulum (ER)-to-mitochondria Ca²⁺ transfer promoted optimal αKG

SUBMITTER: Cardenas C 

PROVIDER: S-EPMC9387586 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature