#14 Organelles + Contact sites

ER function

synthesis/folding/mods/QC of proeins for secretion/PM insertion/organelles, synthesis of lipids/hormones, storage of ions

ER structure

continuous membrane network with branching tubules/sheets continuous with outer nuclear membrane

Highly curved membrane edges stabilized by curvature promoting proteins

very fluid lipids (little cholesterol), no complex carbs/lipid-linked surgars

ER lumen

pH neutral, high Ca2+ bound to proteins, oxidizing environment, chaperones/folding enzymes

Protein folding

3-5aa/sec translated, includes covalent modifications (peptide cleavage, carbohydrate coupling, di-sulfide bond formation), assisted by molecular chaperones

Important for QC (misfolded/aggregates), ER associated degredation, UPR

Golgi function

synthesis of carbohydrates (glycoproteins/polysaccharides), sphingomyelin/sphingoglycolipids, aa modifications, proteolyti

Golgi structure

cis-, medial-, trans-Golgi, stacks of flattened cisternae/tubular connections, transported molecules undergo series of covalent modification as secretory cargo moves cis-to-trans in 15 mins

Transportation

molecules undergo series of covalent mods as cargo moves cis to trans in 15 mins

COP I coat

coat vesicles of forward pathway (ER->golgi)

COPII coat

coat vesicles of retrieval pathway (golgi->ER)

KDEL receptor

binds escaped ER resident proteins in pH dependent manner (aka only occurs in PH of golgi/vesicles, not of ER), shuttles between ER and golgi

Protein sorting

occurs in Golgi, distributes modified proteins/lipids from ER to PM/endosomes/secretory vesicles

M6P

mannose-6-phosphate, marks proteins for delivery to lysosomes

constitutive secretory pathway

contains proteins/lipids that are continuously released from the cell

regulated secretory pathway

for proteins whose release are signal mediated (ex. Insulin)

Trans-golgi network

moves correctly folded proteins from the trans-golgi, constitutive secretion to PM, sorting to other compartments,

Peroxisome structure

single membrane, granular matrix (sometimes crystalline core),

Peroxisome function

carry various enzymes (peroxidases) for catabolism/anabolism, lipid metabolism, redox balance via metabolism of ROS, cell signaling/stress response, pathogen response

Fatty acid oxidation

use O2 to remove hydrogen from substrates

catalase

uses H2O2 to oxidize substrates (remove electrons)

B-oxidation

metabolic breakdown of fatty acids to acetyl-coA

endosomes

intracellular sorting organelles, between PM and TGN via vesicles

endoslysosome

fusion of an endosome with a lysosome to target content for degradation

Lysosome

small (0.2-0.3um diameter) but can change shape/size by fission/fusion, highly acidified with proton pumps, contain hydrolytic enzymes, degrade biological macromolecules mostly from endocytosis/phagocytosis

Secretory pathway

for synthesis/folding/QC of cargo (ER), processing of cargo (Golgi), sorting (TGN), all via vesicular transport (ER->golgi->PM)

Budding

mediated by differently coated vesicles that drive budding via membrane curvature, selective capture of cargo, regulated by small GTPases

Sorting

pH gradient along pathway changes affinities, allowing cargo to detach from receptors at specific pH

Recycling

Incompletely folded proteins retained by association with ER chaperones

Rab proteins

recognize organelles via specific molecules on surface, binding platforms

Specificity

performed by Rab proteins, ensures unique localization of vesicles

Membrane fusion

energy dependant, mediated by SNAREs in both membranes to provide force, regualted by peripheral membranes proteins (Rabs, ATPases)

Endocytosis

internalization of fluids/solutes/macromolecules/PM components and formation of vesicles/vacuoles through membrane fission (Continuous vs triggered)

Endocytic pathway

series of interconnected organelles via which internalized endocytosed cargos are transported by vesicles/fission/fusion

Early endosomes

tubular/vesicular structures at periphery of cytoplasm, pH 6.0-6.5, sorting station for receptors/cargo (uncoupling), Rab5, recycling receptors for ligands leave EE

Maturation

vacuolar elements dissociate from tubules, pH <5.5, Rab7, endosomes associate with microtubules, transported to perinuclear space, addition of Rab9

LDL

endocytosed by cell, dissociates from its receptor in acidic EE, transported to Endolysosome for degradation/release of cholesterol

Recyling endosomes

storage site for PM proteins that are mobilized when needed

Membrane contact sites

closely opposed but not fused membranes with various molecular machineries, affects function of the organelle, can be transient or stable (1s to life-long) varying distance, often involves tetherin

Lipid stress

ceramides accumulate in ER, MCS increase between ER/golgi to transport ceramides out of ER

Nutrient stress

induces mitophagy, causes an isolation membrane to grow from ER to mitochondria

ER/oxidative stress

ROS stress induces increase in mito-ER contacts and protein composition for contacts changes, enriches PERK (reduces mitochondrial mobility),

Apoptosis

promoted by unfolded proteins in ER increases Ca2+ entry into mitochondria