Genetic mutations affecting mitochondrial function in cancer drug resistance

Genes Genomics. 2023 Mar;45(3):261-270. doi: 10.1007/s13258-022-01359-1. Epub 2023 Jan 7.

Abstract

Mitochondria are organelles that serve as a central hub for physiological processes in eukaryotes, including production of ATP, regulation of calcium dependent signaling, generation of ROS, and regulation of apoptosis. Cancer cells undergo metabolic reprogramming in an effort to support their increasing requirements for cell survival, growth, and proliferation, and mitochondria have primary roles in these processes. Because of their central function in survival of cancer cells and drug resistance, mitochondria are an important target in cancer therapy and many drugs targeting mitochondria that target the TCA cycle, apoptosis, metabolic pathway, and generation of ROS have been developed. Continued use of mitochondrial-targeting drugs can lead to resistance due to development of new somatic mutations. Use of drugs is limited due to these mutations, which have been detected in mitochondrial proteins. In this review, we will focus on genetic mutations in mitochondrial target proteins and their function in induction of drug-resistance.

Keywords: Chemotherapy; Drug resistance; Mitochondria targeting drugs; Mutations in mitochondrial proteins.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Drug Resistance, Neoplasm
  • Mitochondria* / metabolism
  • Mutation
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species