MICROSCOPY BIOCHEMISTRY
CREDIT: ADAPTED FROM NAT U RE
Antibody reduces fat in mice Menopause is associated with health problems for women, such as weight gain and loss of bone density. During menopause, levels of follicle-stimulating hormone (FSH) also rise dramatically. An antibody targeting FSH that was previously shown to increase bone mass in mice also reduces body fat and increases metabolism in mice, according to a new study (Nature 2017, DOI: 10.1038/nature22342). The discovery, by two international teams, that blocking FSH in mice directly counteracts many of the symptoms that arise during menopause holds promise for treatments of myriad conditions, such as obesity, osteoporosis, cardiovascular disease, and cancer. FSH is produced by the pituitary gland in both male and female mammals, and, in addition to stimulating the growth of ovarian follicles in females, regulates numerous other reproductive processes. The teams, supervised by Mone Zaidi and Li Sun at the Icahn School of Medicine at Mount Sinai and Clifford J. Rosen at Maine Medical Center Research Institute, used a synthetic mouse antibody that targets a 13-amino-acid sequence of one subunit of FSH. They tested the antibody on populations of female mice that had their ovaries removed—and thus had high FSH levels—and on both male and female mice that were fed high-fat diets. In both cases, treatment with the antibody resulted in fat loss and increased metabolism. Kathleen Gavin, at the University of Colorado School of Medicine, says the results “are very intruiging and definitely worth more extensive study,” although she cautions that their relevance in humans will require substantial additional investigation.—ELIZABETH WILSON
Watching organelles bump into each other Movies show how six types of the membranebound compartments interact in live cells Cells have membrane-bound compartments, called organelles, that allow certain biochemical processes to proceed without interference from other cell chemistry. For example, lipids are synthesized in the endoplasmic reticulum, stored and transported as lipid droplets, oxidized in mitochondria and peroxisomes, and hydrolyzed and recycled in liposomes. Various types of organelles move around in cells and bump into each other to transfer biomolecules and send and receive biochemical signals. But researchers have struggled to analyze the detailed ways in which organelles interact throughout cells over time. Scientists have now made movies in whole cells showing simultaneous interactions of six types of organelles—lysosomes, mitochondria, the endoplasmic reticulum,
microscopy to monitor the fluorescent proteins and dyes point by point in thin slices of the cells. They analyzed organelle motions and contacts over 300 seconds and noted that the numbers of interactions decreased for most organelles in response to nocodazole, a drug that damages organelle-organizing microtubules. Still, this point-by-point imaging with the scanning confocal microscope is slow. To make three-dimensional videos of organelle interactions throughout whole cells, the researchers needed to speed up the imaging considerably. So they used lattice light-sheet microscopy to observe the fluorescent proteins and dyes simultaneously in cell slices. The scientists wrote software to distinguish each of the six monitored wavelengths and assembled those images to construct 3-D images from the slices.
Snapshots of six organelles in a mouse fibroblast cell (small panels) and a merged image showing mutual interactions (right). Scale bars are 10 µm. peroxisomes, Golgi, and lipid droplets (Nature 2017, DOI: 10.1038/nature22369). The work, by Jennifer Lippincott-Schwartz of Janelia Research Campus and coworkers, represents the most comprehensive analysis ever achieved of organelle motions and interactions, called the organelle interactome. The researchers engineered monkey fibroblast cells to express four or five different-colored fluorescent proteins, each designed to localize in one type of organelle. For the other one or two organelles, the scientists added dyes to the cells known to target the desired compartments. The team first used scanning confocal
Among other findings, the movies show that the endoplasmic reticulum is the central organizer of the organelle interactome network and makes the most contacts with the other organelles. The work is a breakthrough that “opens up wide-ranging opportunities for exploring the molecular mechanisms that underpin the organelle community’s dance,” writes Sang-Hee Shim of Korea University in a perspective accompanying the paper. “As the art of cell filmmaking matures, a new branch of systems biology based on images and video footage may emerge.”—STU BORMAN MAY 29, 2017 | CEN.ACS.ORG | C&EN
9
