Title | Mitochondria and Cancer. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Zong, W-X, Rabinowitz, JD, White, E |
Journal | Mol Cell |
Volume | 61 |
Issue | 5 |
Pagination | 667-676 |
Date Published | 2016 Mar 03 |
ISSN | 1097-4164 |
Keywords | Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, DNA, Mitochondrial, Energy Metabolism, Genetic Predisposition to Disease, Humans, Mitochondria, Molecular Targeted Therapy, Mutation, Neoplasms, Signal Transduction |
Abstract | <p>Decades ago, Otto Warburg observed that cancers ferment glucose in the presence of oxygen, suggesting that defects in mitochondrial respiration may be the underlying cause of cancer. We now know that the genetic events that drive aberrant cancer cell proliferation also alter biochemical metabolism, including promoting aerobic glycolysis, but do not typically impair mitochondrial function. Mitochondria supply energy; provide building blocks for new cells; and control redox homeostasis, oncogenic signaling, innate immunity, and apoptosis. Indeed, mitochondrial biogenesis and quality control are often upregulated in cancers. While some cancers have mutations in nuclear-encoded mitochondrial tricarboxylic acid (TCA) cycle enzymes that produce oncogenic metabolites, there is negative selection for pathogenic mitochondrial genome mutations. Eliminating mtDNA limits tumorigenesis, and rare human tumors with mutant mitochondrial genomes are relatively benign. Thus, mitochondria play a central and multifunctional role in malignant tumor progression, and targeting mitochondria provides therapeutic opportunities.</p> |
DOI | 10.1016/j.molcel.2016.02.011 |
Alternate Journal | Mol Cell |
PubMed ID | 26942671 |
PubMed Central ID | PMC4779192 |
Grant List | R01CA163591 / CA / NCI NIH HHS / United States P30CA72720 / CA / NCI NIH HHS / United States R01GM97355 / GM / NIGMS NIH HHS / United States P30 CA072720 / CA / NCI NIH HHS / United States R01 GM097355 / GM / NIGMS NIH HHS / United States R01 CA193970 / CA / NCI NIH HHS / United States R01CA130893 / CA / NCI NIH HHS / United States R01 CA163591 / CA / NCI NIH HHS / United States R01CA188096 / CA / NCI NIH HHS / United States R01CA129536 / CA / NCI NIH HHS / United States R01 CA130893 / CA / NCI NIH HHS / United States R01 CA129536 / CA / NCI NIH HHS / United States R01 CA188096 / CA / NCI NIH HHS / United States R01CA193970 / CA / NCI NIH HHS / United States |