Active mitochondrial respiration in cancer: a target for the drug

Mol Cell Biochem. 2022 Feb;477(2):345-361. doi: 10.1007/s11010-021-04281-4. Epub 2021 Oct 30.

Abstract

The relative contribution of mitochondrial respiration and subsequent energy production in malignant cells has remained controversial to date. Enhanced aerobic glycolysis and impaired mitochondrial respiration have gained more attention in the metabolic study of cancer. In contrast to the popular concept, mitochondria of cancer cells oxidize a diverse array of metabolic fuels to generate a majority of the cellular energy by respiration. Several mitochondrial respiratory chain (MRC) subunits' expressions are critical for the growth, metastasis, and cancer cell invasion. Also, the assembly factors, which regulate the integration of individual MRC complexes into native super-complexes, are upregulated in cancer. Moreover, a series of anti-cancer drugs function by inhibiting respiration and ATP production. In this review, we have specified the roles of mitochondrial fuels, MRC subunits, and super-complex assembly factors that promote active respiration across different cancer types and discussed the potential roles of MRC inhibitor drugs in controlling cancer.

Keywords: Cancer; Drugs; Metabolic fuels; Mitochondria; Respiratory chain subunits; Super-complex.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Drug Delivery Systems*
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Oxidation-Reduction
  • Oxygen Consumption / drug effects*
  • Oxygen Consumption / genetics

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • Electron Transport Complex I