title: Organelle Size Scaling of the Budding Yeast Vacuole by Relative Growth and Inheritance.
abstract: It has long been noted that larger animals have larger organs compared to smaller animals of the same species, a phenomenon termed scaling [1]. Julian Huxley proposed an appealingly simple model of "relative growth"-in which an organ and the whole body grow with their own intrinsic rates [2]-that was invoked to explain scaling in organs from fiddler crab claws to human brains. Because organ size is regulated by complex, unpredictable pathways [3], it remains unclear whether scaling requires feedback mechanisms to regulate organ growth in response to organ or body size. The molecular pathways governing organelle biogenesis are simpler than organogenesis, and therefore organelle size scaling in the cell provides a more tractable case for testing Huxley's model. We ask the question: is it possible for organelle size scaling to arise if organelle growth is independent of organelle or cell size? Using the yeast vacuole as a model, we tested whether mutants defective in vacuole inheritance, vac8Δ and vac17Δ, tune vacuole biogenesis in response to perturbations in vacuole size. In vac8Δ/vac17Δ, vacuole scaling increases with the replicative age of the cell. Furthermore, vac8Δ/vac17Δ cells continued generating vacuole at roughly constant rates even when they had significantly larger vacuoles compared to wild-type. With support from computational modeling, these results suggest there is no feedback between vacuole biogenesis rates and vacuole or cell size. Rather, size scaling is determined by the relative growth rates of the vacuole and the cell, thus representing a cellular version of Huxley's model.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA.
authors.forename: Yee-Hung M
authors.initials: YH
authors.lastname: Chan
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: Lorena
authors.initials: L
authors.lastname: Reyes
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: Saba M
authors.initials: SM
authors.lastname: Sohail
authors.affiliation: Department of Biology, San Francisco State University, 1600 Holloway Avenue, San Francisco, CA 94132, USA.
authors.forename: Nancy K
authors.initials: NK
authors.lastname: Tran
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA; Center for Systems and Synthetic Biology, University of California, San Francisco, 600 16(th) Street, San Francisco, CA 94158, USA. Electronic address: wallace.marshall@ucsf.edu.
authors.forename: Wallace F
authors.initials: WF
authors.lastname: Marshall
mesh_terms: D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D015388:Organelles / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014617:Vacuoles / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C111373:VAC8 protein, S cerevisiae; D033921:Vesicular Transport Proteins