Brazdova 2017 MiP2017
We focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact using the model of isolated brown adipose tissue mitochondria. We demonstrated that biguanides non-specifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate and glycerophosphate dehydrogenases), but only at very high concentrations (10-2 – 10-1 M) that highly exceeded cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also triggered burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, could be toxic for the organism.
We conclude that the favorable effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Diabetes
Tissue;cell: Fat Preparation: Isolated mitochondria
Pathway: F, N, NS HRR: Oxygraph-2k
Affiliations and support
- Dept Bioenergetics, Inst Physiology, Czech Academy Sciences, Prague, Czech Republic. - firstname.lastname@example.org
- Supported by the Grant Agency of the Czech Republic (16-12726S).