This proposal is focused on the transfer of mitochondria during cell division, using the yeast S. cerevisiae as the model system. From previous studies, the PI hypothesized that 1) Arp2/3 complex-mediated actin nucleation on the mitochondrial surface generates the forces for mitochondrial movement; 2) a mitochondrial actin binding protein (mABP) mediates the association with actin cables; 3) polarized actin cables serve as tracks to guide motile organelles from mother cell to bud. During the next funding period, Dr. Pon proposed to test the role of candidate mABP proteins in mediating interactions between mitochondria and actin in vivo and vitro. She will study a putative mitochondrial receptor complex for binding Arp2/3, including its subunit composition and its potential regulatory effects on Arp2/3 and mABP. Dr. Pon will also visualize mitochondrial interactions with actin cables in living cells, and study the effects of mutations that perturb the Arp2/3 complex and actin cable polarity. Finally, Dr. Pon will test her model for actin based mitochondrial motility, by reconstituting the movement using purified organelles and proteins.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
3R01GM045735-11S1
Application #
6946089
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Rodewald, Richard D
Project Start
1993-07-01
Project End
2005-08-31
Budget Start
2003-07-01
Budget End
2005-08-31
Support Year
11
Fiscal Year
2004
Total Cost
$95,764
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Area-Gomez, Estela; de Groof, Ad; Bonilla, Eduardo et al. (2018) A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease. Cell Death Dis 9:335
Garcia, Enrique J; Vevea, Jason D; Pon, Liza A (2018) Lipid droplet autophagy during energy mobilization, lipid homeostasis and protein quality control. Front Biosci (Landmark Ed) 23:1552-1563
Hirabayashi, Yusuke; Kwon, Seok-Kyu; Paek, Hunki et al. (2017) ER-mitochondria tethering by PDZD8 regulates Ca2+ dynamics in mammalian neurons. Science 358:623-630
Pernice, Wolfgang M; Swayne, Theresa C; Boldogh, Istvan R et al. (2017) Mitochondrial Tethers and Their Impact on Lifespan in Budding Yeast. Front Cell Dev Biol 5:120
Pernice, Wolfgang M; Vevea, Jason D; Pon, Liza A (2016) A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae. Nat Commun 7:10595
Higuchi-Sanabria, Ryo; Garcia, Enrique J; Tomoiaga, Delia et al. (2016) Characterization of Fluorescent Proteins for Three- and Four-Color Live-Cell Imaging in S. cerevisiae. PLoS One 11:e0146120
Higuchi-Sanabria, Ryo; Swayne, Theresa C; Boldogh, Istvan R et al. (2016) Imaging of the Actin Cytoskeleton and Mitochondria in Fixed Budding Yeast Cells. Methods Mol Biol 1365:63-81
Higuchi-Sanabria, Ryo; Charalel, Joseph K; Viana, Matheus P et al. (2016) Mitochondrial anchorage and fusion contribute to mitochondrial inheritance and quality control in the budding yeast Saccharomyces cerevisiae. Mol Biol Cell 27:776-87
Higuchi-Sanabria, Ryo; Swayne, Theresa C; Boldogh, Istvan R et al. (2016) Live-Cell Imaging of Mitochondria and the Actin Cytoskeleton in Budding Yeast. Methods Mol Biol 1365:25-62
Vevea, Jason D; Garcia, Enrique J; Chan, Robin B et al. (2015) Role for Lipid Droplet Biogenesis and Microlipophagy in Adaptation to Lipid Imbalance in Yeast. Dev Cell 35:584-599

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