RRC ID 51502
Author Yu Y, Mutlu AS, Liu H, Wang MC.
Title High-throughput screens using photo-highlighting discover BMP signaling in mitochondrial lipid oxidation.
Journal Nat Commun
Abstract High-throughput screens at microscopic resolution can uncover molecular mechanisms of cellular dynamics, but remain technically challenging in live multicellular organisms. Here we present a genetic screening method using photo-highlighting for candidate selection on microscopes. We apply this method to stimulated Raman scattering (SRS) microscopy and systematically identify 57 Caenorhabditis elegans mutants with altered lipid distribution. Four of these mutants target the components of the Bone Morphogenetic Protein (BMP) signaling pathway, revealing that BMP signaling inactivation causes exhaustion of lipid reserves in somatic tissues. Using SRS-based isotope tracing assay to quantitatively track lipid synthesis and mobilization, we discover that the BMP signaling mutants have increased rates of lipid mobilization. Furthermore, this increase is associated with the induction of mitochondrial β-oxidation and mitochondrial fusion. Together these studies demonstrate a photo-highlighting microscopic strategy for genome-scale screens, leading to the discovery of new roles for BMP signaling in linking mitochondrial homeostasis and lipid metabolism.High-throughput genetic screens in animals could benefit from an easy way to mark positive hits. Here the authors introduce photo-highlighting using a photoconvertible fluorescent protein, and in combination with stimulated Raman scattering (SRS) microscopy, define a role for BMP signaling in lipid metabolism in C. elegans.
Volume 8(1)
Pages 865
Published 2017-10-11
DOI 10.1038/s41467-017-00944-3
PII 10.1038/s41467-017-00944-3
PMID 29021566
PMC PMC5636786
MeSH Animals Bone Morphogenetic Proteins / metabolism* Caenorhabditis elegans Homeostasis Lipid Metabolism* Mitochondria / metabolism* Nonlinear Optical Microscopy / methods*
IF 11.878
Times Cited 11
C.elegans tm1133