Lecture11 - Department of Biological Sciences

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Figure 12-6 Molecular Biology of the Cell (© Garland Science 2008)
Figure 12-21a Molecular Biology of the Cell (© Garland Science 2008)
Some Proteins made in the mito.
The Mitochondrial Import Sequence is an amphipathic alpha helix
Figure 12-22 Molecular Biology of the Cell (© Garland Science 2008)
TOM = cytosolic proteins to the intermembrane space
TIM = cytosolic proteins to the matrix and inner membrane
OXA = mitochondrially produced proteins to the intermembrane space
Figure 12-23 Molecular Biology of the Cell (© Garland Science 2008)
An in vitro experiment to determine how mitochondrial transport occurs
Figure 12-24 Molecular Biology of the Cell (© Garland Science 2008)
Cytosolic chaperones like Hsp70 keep proteins
Unfolded until they are fed into the mitochondria
And they contribute to the import process.
Figure 12-25 Molecular Biology of the Cell (© Garland Science 2008)
The RTG Network: a signaling pathway from the mitochondria to the
Nucleus.
Mitochondrial retrograde signaling is a pathway
of communication from mitochondria to the
nucleus under normal and pathophysiological
conditions. The best understood of such
pathways is retrograde signaling in the budding
yeast Saccharomyces cerevisiae. It involves
multiple factors that sense and transmit
mitochondrial signals to effect changes in
nuclear gene expression; these changes lead to
a reconfiguration of metabolism to accommodate
cells to defects in mitochondria. Analysis of
regulatory factors has provided us with a
mechanistic view of regulation of retrograde
signaling. Here we review advances in the yeast
retrograde signaling pathway and highlight its
regulatory factors and regulatory mechanisms,
its physiological functions, and its connection to
nutrient sensing, TOR signaling, and aging.
Aging, the greatest disease of all!
Like many young scientists with a novel idea, Kenyon encountered more skepticism than support in the
early 1990s. Indeed, one fellow scientist, worried that she had gone “over the edge,” warned that if she
continued to insist that aging was subject to genetic regulation, she would soon fall off the Earth altogether.
But her world turned out to be round, not flat. And now firmly anchored as, if not exactly the “queen of aging
research,” then certainly its ace, Kenyon commands no fewer than 386,000 entries on a standard Google
search.
The story is now well-known. One of Kenyon’s lab rotation students —
Ramon Tabtiang — in one of his very first experiments, picked a needle
out of the haystack that is the C. elegans genome. In short, he found a
mutant gene, dubbed daf-2, that made worms live twice as long.
http://www.ucsf.edu/science-cafe/conversations/kenyon/
Peroxisome
Zellweger syndrome
PXR1 is a receptor on the surface of peroxisomes
Peroxisome
-self assembling, 1 day lifespan
-arose due to oxygenation
-proteins translated in cytosol, PTS directs them to peroxisomes
-PTS1 in matrix proteins is usually Ser-Lys-Leu at the C-terminus
-Pex5 is a PTS1 receptor that directs cytoplasmic proteins to per.
-also a PTS2 sequence
-membrane PEX proteins have a different targeting sequence
Peroxisomal Biogenesis
-integral membrane PEX10/12/2 form a receptor/channel on per.
Peroxisomal Biogenesis
-tetramer -> dimer of Pex5
Ines Heiland and Ralf Erdmann
Peroxisomal Biogenesis
Pex11 is involved in peroxisome propagation
Peroxisomal Biogenesis
Ines Heiland and Ralf Erdmann
Peroxisomal Function and Enzymes
50 different enzymes
Lipid metabolism
Hydrogen peroxide breakdown: catalase
Lipid biosynthesis (cholesterol)
Amine and bile acid synthesis
Purine catabolism by urate oxidase
Peroxisomal Function and Enzymes
ß-oxidation of Very Long Chain Fatty Acids (VLCFA)
provides the cell with a major source of metabolic energy
(oxidation of fats mostly occurs in mitos)
Saturated
Unsaturated (“good”)
Peroxisomal Function and Enzymes
50 different enzymes
Lipid metabolism:
ß-oxidation of Very Long Chain Fatty Acids (VLCFA)
-provides the cell with a major source of metabolic energy
Hydrogen peroxide breakdown: catalase
Lipid bisynthesis (cholesterol)
Amine and bile acid synthesis
Purine catabolism by urate oxidase
Figure 12-54 Molecular Biology of the Cell (© Garland Science 2008)
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