title: Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle abundance.
abstract: Fluctuations in organelle abundance can profoundly limit the precision of cell biological processes from secretion to metabolism. We modeled the dynamics of organelle biogenesis and predicted that organelle abundance fluctuations depend strongly on the specific mechanisms that increase or decrease the number of a given organelle. Our model exactly predicts the size of experimentally measured Golgi apparatus and vacuole abundance fluctuations, suggesting that cells tolerate the maximum level of variability generated by the Golgi and vacuole biogenesis pathways. We observe large increases in peroxisome abundance fluctuations when cells are transferred from glucose-rich to fatty acid-rich environments. These increased fluctuations are significantly diminished in mutants lacking peroxisome fission factors, leading us to infer that peroxisome biogenesis switches from de novo synthesis to primarily fission. Our work provides a general framework for exploring stochastic organelle biogenesis and using fluctuations to quantitatively unravel the biophysical pathways that control the abundance of subcellular structures.DOI: http://dx.doi.org/10.7554/eLife.02678.001.
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, United States Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States Howard Hughes Medical Institute, Harvard University, Cambridge, United States.
authors.forename: Shankar
authors.initials: S
authors.lastname: Mukherji
authors.affiliation: FAS Center for Systems Biology, Harvard University, Cambridge, United States Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States Howard Hughes Medical Institute, Harvard University, Cambridge, United States Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States Erin_Oshea@harvard.edu.
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Shea
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D001703:Biophysics; D003470:Culture Media; D005227:Fatty Acids / Q000032:analysis; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D005947:Glucose / Q000032:analysis; D006056:Golgi Apparatus; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008962:Models, Theoretical; D001678:Organelle Biogenesis; D015388:Organelles / Q000378:metabolism*; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015202:Protein Engineering; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles; D015003:Yeasts / Q000235:genetics* / Q000378:metabolism; D000097573:Red Fluorescent Protein
chemical_list: D000426:Alcohol Dehydrogenase; D003470:Culture Media; D005227:Fatty Acids; D005656:Fungal Proteins; D005947:Glucose; D049452:Green Fluorescent Proteins; D006836:Hydro-Lyases; D008164:Luminescent Proteins; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D029701:Saccharomyces cerevisiae Proteins; D000097573:Red Fluorescent Protein; C057183:TEF2 protein, S cerevisiae; C516801:ADH1 protein, S cerevisiae; C586384:HIS3 protein, S cerevisiae
keywords: cell biology; fluctuations; mathematical modeling; organelles; systems biology