The phasor-FLIM fingerprints reveal shifts from OXPHOS to enhanced glycolysis in Huntington Disease

• DOI: 10.1038/srep34755
• Publication Date: 2016-10-07T09:54:48Z
• Authors: Sara Sameni; Adeela Syed; J. Lawrence Marsh; Michelle A. Digman
• Keywords: Huntingtin Protein

Abstract Huntington disease (HD) is an autosomal neurodegenerative disorder caused by the expansion of Polyglutamine (polyQ) in exon 1 Huntingtin protein. Glutamine repeats below 36 are considered normal while above 40 lead to HD. Impairment energy metabolism a common trend pathogenesis; however, this effect not fully understood. Here, we used phasor approach and Fluorescence Lifetime Imaging Microscopy (FLIM) measure changes between free bound fractions NADH as indirect metabolic alteration living cells. Using Phasor-FLIM, pixel maps HEK293 cell lines transgenic Drosophila expressing expanded unexpanded polyQ HTT exon1 eye disc were developed. We found significant shift towards increased NADH, indicating glycolytic state for cells tissues compared control. In nucleus, further lifetime occurs higher suggesting possible synergism dysfunction transcriptional regulation. Our results indicate that HD shifts glycolysis leading oxidative stress death. This powerful label method can be screen native tissue samples potential drug screening.