RT Journal Article
SR Electronic
T1 Coarse-grained model of mitochondrial metabolism enables subcellular flux inference from fluorescence lifetime imaging of NADH
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.20.392225
DO 10.1101/2020.11.20.392225
A1 Xingbo Yang
A1 Daniel J. Needleman
YR 2021
UL http://biorxiv.org/content/early/2021/04/07/2020.11.20.392225.abstract
AB Mitochondrial metabolism is of central importance to diverse aspects of cell and developmental biology. Defects in mitochondria are associated with many diseases, including cancer, neuropathology, and infertility. Our understanding of mitochondrial metabolism in situ and dysfunction in diseases are limited by the lack of techniques to measure mitochondrial metabolic fluxes with sufficient spatiotemporal resolution. Herein, we develop a new method to infer mitochondrial metabolic fluxes in living cells with subcellular resolution from fluorescence lifetime imaging of NADH. This result is based on the use of a coarse-grained model of mitochondrial metabolism. We test the model in mouse oocytes subject to a wide variety of perturbations by comparing predicted fluxes through the electron transport chain to direct measurements of oxygen consumption rate. Using this method, we discover a subcellular spatial gradient of mitochondrial metabolic flux in mouse oocytes. This label-free technique will help provide new insights into the spatiotemporal regulation of metabolic fluxes in developing organisms and in diseases.Competing Interest StatementThe authors have declared no competing interest.