Mitochondrial targets of metformin-Are they physiologically relevant?

Biofactors. 2019 Sep;45(5):703-711. doi: 10.1002/biof.1548. Epub 2019 Jul 25.

Abstract

Metformin is the most widely prescribed treatment of hyperglycemia and type II diabetes since 1970s. During the last 15 years, its popularity increased due to epidemiological evidence, that metformin administration reduces incidence of cancer. However, despite the ongoing effort of many researchers, the molecular mechanisms underlying antihyperglycemic or antineoplastic action of metformin remain elusive. Most frequently, metformin is associated with modulation of mitochondrial metabolism leading to lowering of blood glucose or activation of antitumorigenic pathways. Here we review the reported effects of metformin on mitochondrial metabolism and their potential relevance as effective molecular targets with beneficial therapeutic outcome.

Keywords: AMPK; metformin; mitochondria; oxidative phosphorylation.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism
  • Gene Expression Regulation / drug effects
  • Glycerolphosphate Dehydrogenase / genetics
  • Glycerolphosphate Dehydrogenase / metabolism
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Hyperglycemia / pathology
  • Hypoglycemic Agents / therapeutic use*
  • Metformin / therapeutic use*
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / prevention & control*
  • Oxidative Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Reactive Oxygen Species
  • Metformin
  • Glycerolphosphate Dehydrogenase
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • Electron Transport Complex I