--- module: 082-01 language: en chapter: 82 title: "Cell Architecture, Organelles, Cytoskeleton, Trafficking, and the Cell Cycle" module_title: "Membrane systems, organelles, protein trafficking, and cellular quality control" source_sha256: d513cf303392b6880370cc475c70393bdfc8fe118effee7bf8d591d6c70f730a --- # Membrane systems, organelles, and quality control ## Compartments and the plasma membrane ### Compartments run incompatible reactions together ### Selective transport keeps distinct compositions ### Wrong place, wrong time, or poor removal causes disease ### Fluid bilayer with asymmetric leaflets #### Phosphatidylserine normally on cytosolic leaflet #### Externalised: apoptosis mark, platelet coagulation ### Glycocalyx: protection, recognition, adhesion ## Membrane transport ### Small hydrophobic molecules diffuse through lipid ### Channels: rapid flow down gradients ### Carriers: facilitated diffusion or coupled transport ### Pumps use chemical energy to move solutes uphill ### Endocytosis and exocytosis are regulated ## Nucleus and condensates ### Separates transcription from translation ### Nuclear pores gate large molecules #### Receptors read localisation and export signals #### Ran cycle sets direction ### Euchromatin active, heterochromatin compact ### Lamina anchors chromatin and supports mechanics #### Lamin mutations: dystrophy, cardiomyopathy, early ageing ### Nucleolus assembles ribosomal subunits ### Phase separation concentrates without membrane #### Pathological persistence promotes aggregation ## Protein targeting and the endoplasmic reticulum ### Polypeptide signals set destination ### Signal-recognition particle docks ribosome at rough ER #### Synthesis resumes through translocon ### Folding, disulfide bonds, initial glycosylation ### Associated degradation of misfolded proteins #### Only assembled cargo exits to Golgi ### Unfolded-protein response #### Less translation, more chaperones, larger ER #### Failure: inflammation or apoptosis #### Secretory cells depend on it most ### Smooth ER: lipids, steroids, detoxification, calcium #### Sarcoplasmic reticulum controls contraction #### Hepatic expansion alters drug interactions ## Golgi, endosomes, and lysosomes ### Golgi remodels carbohydrate chains ### Trans-Golgi network sorts cargo ### Mannose-six-phosphate tags lysosomal enzymes #### Mistargeting: enzyme secreted, substrate stored ### Affected tissues set by load and vulnerability #### Neurons cannot dilute by division ### Early endosome acidity frees ligand #### Recycling restores responsiveness #### Lysosomal degradation limits signalling ### Pathogens and toxins exploit these routes ## Degradation: autophagy and proteasome ### Acid hydrolases digest macromolecules ### Autophagosomes fuse with lysosomes #### Basal removal, starvation recycling #### Selective forms such as mitophagy ### Polyubiquitin marks proteasome substrates #### Ubiquitin ligases confer specificity #### Controls signalling and cycle regulators #### Peptides feed class one antigen presentation ## Mitochondria and peroxisomes ### Also regulate metabolism, calcium, apoptosis ### Inner membrane cristae and proton pumping #### Adenosine triphosphate synthase uses the gradient ### Most proteins nuclear encoded and imported ### Fusion shares contents, fission removes damage #### High-energy tissues most affected ### Peroxisomes shorten very-long-chain fatty acids #### Catalase converts hydrogen peroxide #### Import includes fully folded proteins ## Contact sites, trafficking, and secretion ### Contact sites exchange lipids, calcium, signals ### Organelles form a network, not isolated bags ### Coats bend membranes and select cargo ### Rabs specify identity, SNAREs drive fusion ### Constitutive versus regulated secretion #### Calcium often triggers regulated release #### Membrane retrieved and reused after fusion ## Integrated quality control ### Repairable damage versus irrecoverable failure ### Successful compensation: adaptation ### Failure: senescence, apoptosis, necrosis