Volume 2 Supplement 1
Effects of biguanides on oxidative phosphorylation
- Judy Hirst1
© Hirst; licensee BioMed Central Ltd. 2014
Published: 28 May 2014
Metformin, and the related biguanides buformin and phenformin, have been proposed to act by inhibiting respiratory complex I, causing the cellular energetic stress that activates AMP-kinase and initiates a multitude of cell-lineage-specific effects, including inhibition of gluconeogenesis in hepatocytes. However, the molecular mechanism of biguanide action on complex I is not known, limiting understanding of pharmacological effects on this proposed primary target. Biguanides have also been proposed to affect reactive oxygen species production in cells, a respiratory-chain linked effect - but there is no consensus even on whether they increase or decrease it. In this talk I will discuss the results of experiments on a hierarchy of systems, from purified respiratory enzymes and membrane preparations, to mitochondria and cells, to define the functional effects of biguanides on the oxidative phosphorylation system. The aim is to define and link the molecular effects of biguanides on specific enzymes to their known effects on cellular and signalling pathways.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.