Mitochondrial fusion supports increased oxidative phosphorylation during cell proliferation

Cong Hui Yao, Rencheng Wang, Yahui Wang, Che Pei Kung, Jason D. Weber, Gary J. Patti

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting aspartate to consuming it. Transforming fibroblasts with the Ras oncogene induced mitochondrial biogenesis, which further elevated OXPHOS. Notably, transformed fibroblasts continued to have elongated mitochondria and their proliferation remained sensitive to inhibition of Mfn2. Our results suggest that cell proliferation requires increased OXPHOS as supported by mitochondrial fusion.

Original languageEnglish
Article numbere41351
JournaleLife
Volume8
DOIs
StatePublished - Jan 29 2019

Keywords

  • cancer
  • cancer biology
  • cell biology
  • cell proliferation
  • human
  • metabolism
  • mitochondrial fusion
  • mouse
  • oxidative phosphorylation
  • warburg effect

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