BDNF increases rat brain mitochondrial respiratory coupling at complex I, but not complex II.
Brain-derived neurotrophic factor (BDNF) governs both the selective survival of neurons during development and the experience-based regulation of synaptic strength throughout life. BDNF produced a concentration-dependent increase in the respiratory control index (RCI, a measure of the efficiency of respiratory coupling, ATP synthesis and organelle integrity) of rat brain mitochondria. This effect was mediated via a MAP kinase pathway and highly specific for oxidation of glutamate plus malate (complex I) by brain mitochondria. The oxidation by brain mitochondria of the complex II substrate succinate was unaffected by BDNF. The failure of BDNF to modify respiratory activity associated with mitochondrial preparations isolated from rat liver indicates that the actions of the neurotrophin are tissue specific. BDNF also increased the RCI values associated with Ca2+ -induced respiration to a similar extent. This is the first demonstration that BDNF, in addition to modifying neuronal plasticity, can modify brain metabolism and the efficiency of oxygen utilization. The finding that neurotrophins can alter mitochondrial oxidative efficiency has important implications for neurodegenerative and psychiatric diseases.
Markham
A
A
Institute of Pharmacy, Chemistry and Biomedical Sciences, School of Health, Natural and Social Sciences, University of Sunderland, Wharncliffe Street, SR1 3SD, UK.
Cameron
I
I
Franklin
P
P
Spedding
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D042967:Electron Transport Complex I / Q000096:biosynthesis* / Q000378:metabolism; D042963:Electron Transport Complex II / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; C478189:respiratory complex II; D042963:Electron Transport Complex II; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I