Mitochondrial alterations during carcinogenesis: a review of metabolic transformation and targets for anticancer treatments

Adv Cancer Res. 2013:119:127-60. doi: 10.1016/B978-0-12-407190-2.00004-6.

Abstract

Mitochondria play important roles in multiple cellular processes including energy metabolism, cell death, and aging. Regulated energy production and utilization are critical in maintaining energy homeostasis in normal cells and functional organs. However, mitochondria go through a series of morphological and functional alterations during carcinogenesis. The metabolic profile in transformed cells is altered to accommodate their fast proliferation, confer resistance to cell death, or facilitate metastasis. These transformations also provide targets for anticancer treatment at different levels. In this review, we discuss the major modifications in cell metabolism during carcinogenesis, including energy metabolism, apoptotic and autophagic cell death, adaptation of tumor microenvironment, and metastasis. We also summarize some of the main metabolic targets for treatments.

Keywords: HIF1; Hypoxia; Microenvironment; Mitochondria; ROS; Respiration; Warburg; mtDNA.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Carcinogenesis*
  • Cell Proliferation
  • Cell Transformation, Neoplastic*
  • DNA, Mitochondrial / genetics
  • Disease Progression
  • Electron Transport*
  • Energy Metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Neoplasm Metastasis
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Reactive Oxygen Species
  • Transcription, Genetic

Substances

  • Antineoplastic Agents
  • DNA, Mitochondrial
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Reactive Oxygen Species