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z:Cell 300 > Lecture 16: Peroxisomes > Flashcards

Lecture 16: Peroxisomes Flashcards

1
Q

peroxisomes carry out a ____

A

variety of essential functions in a wide spectrum of organisms

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2
Q

peroxisome (descr.)

A

single membrane organelle that has fine granular matrix

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3
Q

peroxisomes are generally _____

A

spherical with diameters of 0.2 to 1 um

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4
Q

number and composition of peroxisomes _____

A

vary widely depending on physiological needs

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5
Q

peroxisomes are distributed _____

A

evenly in human cell

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6
Q

peroxisomes size depends on ____

A

diet of organism

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7
Q

peroxisomes under EM

A

electron dense surrounded by membrane

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8
Q

peroxisomes are organelles that ____

A

use molecular oxygen and hydrogen peroxide to carry out oxidative reactions

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9
Q

peroxisomes: 2 essential enzymes

A

-oxidase (produces H2O2)
-catalase (decomposes H2O2)

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10
Q

oxidase reaction

A

RH + O2 -> R + H2O2 (produces H2O2)

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11
Q

catalase reaction

A

decomposes H2O2

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12
Q

peroxisomes detoxify _____

A

several toxic molecules (ex. ethanol)

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13
Q

peroxidation (def.)

A

H2O2+ R’H2 —> R’+ 2H2O

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14
Q

site of lipid metabolism in mammalian cells

A

mitochondria & peroxisomes

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15
Q

site of B-oxidation of long chain fatty acids in mammalian cells

A

mitochondria & peroxisomes

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16
Q

site of bile synthesis in mammalian cells

A

mitochondria & peroxisomes

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17
Q

site of B-oxidation of long chain fatty acids in yeast cells

A

peroxisomes

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18
Q

peroxisomes are central to _______

A

lipid metabolism

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19
Q

Peroxisomes control ____

A

extent of oxidative stress with catalase by controlling levels of reactive oxygen species (ROS)

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20
Q

peroxisome function requires tethering to _____ (2)

A

lipid sources (lipid droplets)
lipid metabolizing organelles (mitochondria,ER)

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21
Q

lipid metabolizing organelles (2)

A

mitochondria
ER

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22
Q

size of peroxisome = how ____

A

metabolically active the cell is

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23
Q

2 types of disorders with peroxisomes

A

-protein deficiencies
-deficiencies in biogenesis of peroxisomes

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24
Q

peroxisomes disorders help to identify ____

A

human genes required for peroxisome function

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25
Q

class of inherited disorders that affect biogenesis of peroxisomes

A

Zellweger Spectrum Disorders

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26
Q

peroxisomes are required for proper ____

A

human development and physiology

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27
Q

peroxisomes function + neural defects

A

they catalyze 1st reaction in formation of plasmalogens (phospholipids in myelin)
defects in peroxisomes biogenesis -> neural defects

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28
Q

peroxisomes are the signaling platform for ____

A

antiviral response

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29
Q

immunity: increasing peroxisomes leads to ____ by ___

A

increased capacity of innate immunity
inhibiting RNA viral replication

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30
Q

Interferon (def.)

A

group of signaling proteins made and released by host cells in response to the presence of several viruses
-part of innate immunity

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31
Q

peroxisomes and interferon relationship

A

increase peroxisomes = increase activity of interferon simulated gene

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32
Q

interferon simulated gene (ISGs) (def.)

A

a gene that can be expressed in response to stimulation by interferon

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33
Q

Zellweger Spectrum Disorders (ZSS) and other peroxisomal diseases leads to the accumulation of _____

A

very long chain fatty acids in blood and many tissues

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34
Q

ZSS is the result from defects in at least of how many pex genes?

A

14

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35
Q

protein targeting to peroxisomes involves two pathways: _____

A

-direct import from cytoplasm
-import machinery of the ER

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36
Q

peroxisomes lack _____ and _____

A

genome
protein synthesis machinery

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37
Q

all peroxisomal protein are encoded in _____ and synthesized by ____

A

nucleus
ribosomes in cytosol

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38
Q

peroxisomes are completely dependent on ____ for biogenesis

A

completely dependent on import of protein for biogenesis

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39
Q

signal needed for the import of peroxisome matrix proteins

A

Peroxisome Targeting Signal (PTS)

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40
Q

two types of signals (PTS) for import of peroxisome matrix proteins

A

-PTS1
-PTS2

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41
Q

most common PTS signal

A

PTS1

42
Q

PTS1 (descr.)

A

conserved C-terminal tripeptide sequence (SKL)

43
Q

PTS1 is the primary _____

A

targeting signal used by majority of matrix proteins

44
Q

PTS1 is ___ and ____ for targeting to peroxisomes (needed and enough for transport)

A

essential and sufficient

45
Q

GTP with PTS1 motif is transported where?

A

peroxisomes

46
Q

PTS2 (descr.)

A

conserved N-terminal nonapeptide (9 a.a.)

47
Q

PTS2 sequence

A

(R/K)(L/V/I)(X5)(H/Q)(L/A)

48
Q

PTS2 is used by ____

A

smaller subset of matrix proteins

49
Q

characterization of pex targeting mutants is done with_____ because ____

A

yeast
B-oxidation of fatty acids only occurs in peroxisomes

50
Q

characterization of pex targeting mutants method

A

*Mutagenize yeast cells in culture
*Divide in many aliquots
*Plate each aliquot on standard plate
*Replica plate
*Identify mutants that grow on complete medium, but fail to grow on plates with long chain fatty acids as sole carbon source

51
Q

two proteins recognize proteins that have PTS1 or PTS2 bearing proteins

A

Pex5p
Pex7p

52
Q

Pex5/7 ____ produces Pex5/7p (___)

A

gene
protein

53
Q

Pex5p recognizes protein with _____ targeting signal

A

PTS1

54
Q

Pex7p recognizes protein with _____ targeting signal

A

PTS2

55
Q

recognition of PTS2 involves ____ and _____

A

Pex7p
factor X (varies from species to species)

56
Q

recognition of PTS1 involves ____

A

Pex5p

57
Q

Pex5p and Pex7p require ___

A

docking proteins/channels/translocation complex

58
Q

Pex13p/Pex14p form complex exposed to ___

A

cytosolic surface of peroxisomal membrane

59
Q

Pex13p/Pex14p are resistant to extraction with ___ so they are _____

A

-high pH carbonate buffers (still in pellet)
integral membrane proteins

60
Q

peroxisome extraction: pellet

A

imbedded with membrane

61
Q

peroxisome extraction: supernatant

A

inside the peroxisome

62
Q

Pex14p binds to ___

A

both PTS receptors (Pex5p and Pex7p)

63
Q

Pex14p is the docking site for both _____

A

Pex5p and Pex7p complexes

64
Q

overall pex14p mechanism

A

pex14 binds and internalizes PTS receptors (like a channel) with the help of other membrane proteins

65
Q

import of matrix proteins is ___ and doesn’t require ___ (not like ER)

A

post-translational
unfolding

66
Q

matrix proteins are stabilized with ____ before import into peroxisome

A

disulfide bonds and chemical cross-linkers

67
Q

size of several matrix proteins

A

> 450 kDa (ex. catalase)

68
Q

9nm gold particles with PTS1 is where?

A

peroxisome

69
Q

Pex5p/7p found in the matrix of peroxisomes suggest that ___

A

PTS receptors are co-imported with their substrates

70
Q

Pex5 shuttling between cytosol and matrix steps

A

1) Pex5 forms complex with proteins with PTS1
2)Pex5 docks on peroxisomal membrane through Pex14
3)Part or all of complex translocated into peroxisomal matrix
4) Cargo released in matrix
5) Pex5p is mono-ubiquinated
6) Pex5p is de-unbiquinated and exported back to cytosol in ATP-dependent process

71
Q

Pex5p is _____ and then ______ to be exported back in cytosol

A

mono-ubiquinated
de-ubiquinated

72
Q

Different types of ubiquination have ___

A

drastically different function

73
Q

polyubiquination leads to ____

A

protein degradation

74
Q

import process of PTS receptors is poor understood but ____

A

Pex5 oligomer may act as a transient pore

75
Q

polysome (def.)

A

group of ribosomes bound to an mRNA molecule like “beads” on a “thread

76
Q

most integral membrane proteins of peroxisome are synthesized _____

A

on free polysome

77
Q

integral membrane proteins are targeted and inserted _____

A

post-translationally into peroxisomal membrane

78
Q

integral membrane proteins are targeted to peroxisome by various ____

A

membrane related PTS (mPTS)

79
Q

mPTS have no ____

A

clear consensus sequence

80
Q

hydrophobic trans-membrane segments of integral membrane proteins interact with ____

A

specific chaperone to prevent aggregation

81
Q

integral membrane proteins and chaperone form ____ that is then _____

A

complex
targeted to receptor on peroxisomal membrane

82
Q

PMP stands for ___

A

peroxisomal membrane proteins

83
Q

chaperone/transporter for peroxisomal membrane proteins

A

pex19p

84
Q

receptor for peroxisomal membrane proteins

A

pex3p

85
Q

some organisms require an additional membrane protein receptor:

A

pex16p

86
Q

PMP inserted into membrane through what mechanism?

A

unknown mechanism

87
Q

Mature peroxisomes are generated by the uptake of ____

A

membrane and matrix proteins to distinct intermediates

88
Q

peroxins (def.)

A

several protein families found in peroxisomes

89
Q

peroxisome biogenesis method

A

1) early peroxins (ex. pex3p) are targeted to ER and translocated by Sec61p complex
2) peroxins are sorted to specific pre-peroxisomal domains within ER then exported into small vesicles/pre-peroxisomes
3)additional PMPs imported into pre-peroxisomes
4) additional matrix proteins imported to form peroxisomes
5) peroxisomes continue to grow by fission

90
Q

1st peroxins that are used to make peroxisomes

A

pex3p - receptor for integral membrane protein

91
Q

pre-peroxisomes also called___

A

ghosts

92
Q

pre-peroxisomes become peroxisomes by the addition of ____ after ___

A

matrix proteins
integral proteins

93
Q

organelle the contributes membranes for de novo peroxisome biogenesis

A

ER

94
Q

Yeast: Peroxisomes originate from
modifying vesicular pathways at the ___

A

ER

95
Q

Mammals: Peroxisomes originate from
combination of modifying vesicular pathways at the ____

A

ER and mitochondria

96
Q

____ is a key factor for the formation of pre-peroxisomal vesicles

A

Pex3

97
Q

lipid droplets are tethered to peroxisomes by tethering protein: ____

A

spastin

98
Q

effect of lipid droplet tethering to peroxisomes on lipid metabolism (2)

A

1) decrease of the size of a lipid droplet over time
2) degradation of lipids from the droplet accelerates

99
Q

spastin knockdown with RNAi result

A

reduced lipid transfer to peroxisomes

100
Q

glycosome (def.)

A

variant of peroxisome

101
Q

Trypanosoma brucei (the parasite that causes ____) compartmentalizes glycolysis in the _____

A

sleeping sickness
glycosome

102
Q

Identification of divergent T. brucei Pex3 led to the discovery that _____

A

glycosome biogenesis is essential for parasite growth

z:Cell 300 (17 decks)

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