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Archives of Industrial Biotechnology | Volume 2
May 14-15, 2018 | Montreal, Canada
World Yeast Congress
T
he immediate responses to inhibitionof phosphatidylcholine
(PC) biosynthesis in yeast are altered phospholipid levels,
slow growth, and defects in the morphology and localization of
ER andmitochondria. With chronic lipid imbalance, yeast adapt.
We find that lipid droplet (LD) biogenesis is up-regulated in yeast
undergoing lipid imbalanceand is required for adaptationto lipid
imbalance. We confirmed that the Unfolded Protein Response,
a stress response pathway that is activated by accumulation of
unfolded ER proteins, is activated by this lipid stress. We also
find that LDs form at ER aggregates, contain polyubiquitinated
proteins and an ER chaperone, and are degraded in the
vacuole by a process resembling microautophagy. This process,
microlipophagy, is required for restoration of organelle
morphology and cell growth during adaptation to lipid stress.
Microlipophagy does not require a core macroautophagy gene,
ATG7, but does requires ESCRT components. It also requires a
newly identified class E VPS protein that localizes to ER and is
up-regulated by lipid imbalance. In complementary studies, we
detect elevated lipid droplet biogenesis, ER stress, and defects
in ER proteins that are essential for excitation contraction
coupling in a mouse model for a congenital muscular dystrophy
produced by defects in PC biosynthesis. Using super-resolution
microscopy, we find that unfolded ER proteins are associated
with lipid droplets. Thus, the ER proteostasis pathway that
we identified in yeast occurs in mammalian cells and may
contribute to protein quality control in human disease
Speaker Biography
Liza Pon studied mitochondrial function in steroid hormone biosynthesis as a pre-
doctoral student in the laboratory of N.R. Orme-Johnson at Tufts University (1982-
1987). As an NRSA Postdoctoral Fellow with Gottfried Schatz at the University of Basel,
she studied protein import into mitochondria (1987 -1990). Dr. Pon established her
own laboratory in 1990 at Columbia University, where she is currently Professor of
Pathology and Cell Biology and the Institute of Human Nutrition, and Director of the
Confocal and Specialized Microscopy Shared Resource. The focal point of her research
is organelle quality control, interaction of mitochondria with the cytoskeleton and
other organelles, and how these processes affect cellular fitness and lifespan.
e:
lap5@cumc.columbia.eduLiza A Pon
Columbia University, USA
Role for lipid droplet biogenesis and microlipophagy in adaptation to lipid imbalance
in yeast and in a mouse model for human disease