Exam 3- Ch.11 Protein Sorting and Transport

Chapter 11: Protein Sorting and Transport

The Endoplasmic Reticulum (ER)

• Structural Basis:

  • Comprises membrane-enclosed tubules and sacs (cisternae).

  • Extends from the nuclear membrane throughout the cytoplasm.

• Scale in Eukaryotic Cells:

  • Largest organelle in most eukaryotic cells.

• Distinct Membrane Domains:

  • Two contiguous membrane domains within the ER serve different cellular functions.

• Two Types (ER Domains):

  • Rough ER (RER):

    • Ribosome-studded.

    • Site of protein synthesis for secreted, membrane-bound, and lysosomal proteins.

  • Smooth ER (SER):

    • Ribosome-free.

    • Functions in lipid synthesis, detoxification, and calcium storage.

ER and Protein Synthesis

• Discovery of ER's Role:

  • George Palade and colleagues in the 1960s studied pancreatic acinar cells secreting digestive enzymes.

  • Used a pulse-chase experiment with radioactive amino acids.

• Pulse-Chase Experiment Results:

  • Pulse: Radiolabeled proteins detected in the rough ER.

  • Chase: Proteins moved to the Golgi apparatus.

  • Longer Chase: Proteins reached the cell surface via secretory vesicles, releasing contents outside the cell.

• Secretory Pathway Definition:

  • Rough ER → Golgi → Secretory vesicles → Cell exterior.

The Secretory Pathway

• Radiolabeled Protein Movement:

  • 3-minute pulse label: Radiolabeled protein in the rough ER.

  • 7-minute chase: Protein moves to the Golgi apparatus.

  • 120-minute chase: Protein reaches secretory vesicles.

Protein Sorting

• Site of Synthesis:

  • All proteins are synthesized by ribosomes in the cytoplasm.

• Sorting Dependence:

  • Sorting depends on signal sequences within the protein.

• Types of Sorting:

  • Cytosolic Proteins:

    • No signal; remain in the cytoplasm.

  • Co-translational Sorting:

    • Occurs during synthesis.

    • Proteins enter the ER via signal peptides and SRP-mediated pathway.

    • Destined for ER, Golgi, plasma membrane, lysosomes, or secretion.

  • Post-translational Sorting:

    • Occurs after translation is complete.

    • Proteins are imported into organelles like the nucleus, mitochondria, peroxisomes, or chloroplasts using specific targeting signals.

Signal Hypothesis

• Proposed by:

  • Günter Blobel and David Sabatini in 1971.

• Definition:

  • A short peptide sequence located at the N-terminus of proteins destined for the endoplasmic reticulum (ER).

  • Also called the ER signal peptide.

Key Features of Signal Peptide on ER

• Composition:

  • Typically, 15–30 amino acids long.

  • Most signal sequences contain a stretch of hydrophobic amino acids preceded by basic residues.

• Regions:

  • N-region: 1–5 positively charged residues (e.g., arginine, lysine).

  • H-region: Central hydrophobic core (6–15 nonpolar residues).

  • C-region: Polar region with a cleavage site (recognized by signal peptidase).

Cotranslational Targeting of Secretory Proteins to the ER

1. Signal Sequence Recognition:

   • As the signal sequence emerges from the ribosome, it is recognized and bound by the signal recognition particle (SRP).

2. SRP Escort:

   • The SRP escorts the complex to the ER membrane where it binds to the SRP receptor.

3. Translocon Binding:

   • The SRP is released, the ribosome binds to the translocon, and insertion of the signal sequence opens the translocon.

   • Translation resumes, and the signal sequence is cleaved by signal peptidase.

Structure of the Translocon

• The translocon consists of three transmembrane subunits.

Post-Translational Translocation of Proteins into ER

1. Protein Synthesis:

   • Protein fully synthesized in the cytosol (on free ribosomes).

2. Targeting Signal:

   • Targeting signal within the protein directs it to the correct organelle.

3. Chaperone Binding:

   • Chaperones keep the protein unfolded → Receptor on the organelle (e.g., mitochondria, nucleus, peroxisome) recognizes the signal.

4. Organelle Import:

   • Protein imported into the organelle via translocase complex, then folded and activated inside.

5. Translocon Function:

   • The translocon, a complex of three transmembrane proteins (Sec61 proteins), facilitates protein transfer through the ER membrane.

Post-Translational Protein Destinations in ER

• Mitochondria:

  • via TOM/TIM complexes

• Nucleus:

  • via nuclear pore (with NLS)

• Peroxisomes:

  • via peroxisomal targeting signals (PTS1/PTS2)

• Chloroplasts:

  • via TOC/TIC complexes (in plants)

Insertion of Transmembrane Proteins

• Distinct Pathway:

  • Proteins bound for the plasma membrane or organelle membranes take a unique route.

• ER Membrane Insertion:

  • Rather than being released into the ER lumen, proteins for membranes integrate into the ER membrane initially.

• Common Journey:

  • From the ER membrane, these proteins follow the standard path: ER → Golgi → plasma membrane or lysosomes, existing as integral membrane components.

Hydrophobic Embedding

• Integral membrane proteins use hydrophobic sequences, typically α-helical regions with 20–25 hydrophobic amino acids.

• Diversity in Insertion:

  • Integral membrane proteins display diversity; some span the membrane once, while others have multiple membrane-spanning regions.

• Orientation Variations:

  • These proteins may orient with the carboxy terminus on the cytosolic side or the amino terminus exposed to the cytosol, determined during translocation into the ER.

Orientations of Membrane Proteins

• Integral membrane proteins span the membrane via α-helical regions of 20–25 hydrophobic amino acids, which can be inserted in a variety of orientations.

• Examples of proteins that have single or multiple membrane-spanning regions with different orientations (N-terminus or C-terminus on the cytosolic side).

Topology of the Secretory Pathway

• The ER lumen's equivalence to the cell's exterior dictates the exposure of domains in plasma membrane proteins.

Insertion of a Membrane Protein with a Cleavable Signal Sequence

• Translocation of the polypeptide chain across the membrane is halted when the translocon recognizes a transmembrane sequence.

• This allows the protein to exit the translocon laterally and become anchored in the ER membrane.

Insertion of Membrane Proteins via Internal Transmembrane Sequences

• Internal transmembrane sequences can lead to the insertion of polypeptide chains in either orientation in the ER membrane.

• The transmembrane sequence directs insertion of the polypeptide such that its amino (N) terminus is exposed on the cytosolic side.

• The transmembrane sequence exits the translocon to anchor the protein in the lipid bilayer, and the remainder of the polypeptide chain is translocated into the ER as translation proceeds.

Insertion of a Protein That Spans the Membrane Multiple Times

• Diagram illustrating how multiple transmembrane sequences are inserted into the ER membrane.

Post Translational Insertion of a Protein with a C-Terminal Transmembrane Sequence

• Diagram illustrating how a protein with a C-terminal transmembrane sequence is inserted into the ER membrane via TRC40 and GET1-GET2.

Diverse Functions of ER

• Protein folding

• Assembly of multisubunit proteins

• Disulfide bond formation

• N-linked glycosylation

• Addition of glycolipid anchors

Protein Folding in ER

• Chaperones:

  • e.g., BiP (Binding immunoglobulin Protein)

  • Prevent misfolding and aggregation

• Protein Disulfide Isomerase (PDI):

  • Catalyzes disulfide bond formation for structural stability

• Calnexin & Calreticulin:

  • Assist folding of glycoproteins by binding to specific sugar residues

Protein Folding in the ER

• Chaperone-Mediated Folding:

  • Unfolded polypeptide chains entering the ER fold into their three-dimensional conformations, assisted by chaperones like Hsp70, particularly BiP.

Disulfide Bond Formation

• Protein Disulfide Isomerase (PDI) catalyzes disulfide bond formation between cysteine residues.

• The oxidizing environment of the ER favors disulfide $(S—S)$ bonds.

• In contrast, the cytosol’s reducing environment keeps cysteines in the reduced $(—SH)$ form.

Glycosylation

• Definition:

  • Addition of sugar chains (oligosaccharides) to proteins.

• Process:

  • Proteins undergo N-linked glycosylation on specific asparagine residues during translation in the ER.

• Synthesis on Dolichol:

  • The oligosaccharide is synthesized on a lipid (dolichol) carrier.

• Significance of Glycosylation:

  • Glycosylation plays a crucial role by preventing protein aggregation in the ER and signaling for correct protein folding and sorting in the secretory pathway.

Addition of GPI Anchors

• Attachment:

  • Proteins linked to the plasma membrane via glycolipids known as GPI anchors.

• Assembly:

  • GPI anchors are assembled in the ER membrane.

• Attachment Mechanism:

  • Proteins exchange their C-terminal hydrophobic sequence for a GPI anchor, connecting them to the membrane.

• Transport:

  • Transported to the cell surface through the secretory pathway.

• Orientation:

  • GPI-anchored proteins position with their GPI anchor outside, attaching to the plasma membrane.

Quality Control in ER

• Key Players:

  • Chaperones (e.g., BiP, calnexin, calreticulin)

  • Protein disulfide isomerase (PDI)

  • Glycosylation tags used as folding indicators

• Process

  1. Folding monitored during and after synthesis

  2. Misfolded proteins retained in ER

  3. If irreparable → targeted for ER-associated degradation (ERAD)

Quality control in ER – ER Associated Degradation (ERAD)

• Recognition:

  • Chaperones (e.g., BiP, calnexin) identify misfolded proteins

• Retrotranslocation:

  • Misfolded proteins are moved from the ER lumen back into the cytosol via a translocon complex (e.g., Derlin, HRD1)

• Ubiquitination:

  • Proteins are tagged with ubiquitin by E3 ubiquitin ligases (e.g., HRD1)

• Degradation:

  • Tagged proteins are degraded by the 26S proteasome in the cytosol

Quality Control in ER - Glycoprotein Folding Pathway

• Process:

  • Chaperones recognize partially processed oligosaccharides on glycoproteins, assisting correct folding.

• Outcome:

  • Correctly folded glycoproteins proceed to the Golgi; misfolded ones are targeted for ERAD and degraded in the proteasome.

Quality Control in ER - Unfolded Protein Response (UPR)

• Purpose:

  • Monitors unfolded proteins and adjusts ER folding capacity.

• Triggers:

  • Activated by accumulation of unfolded proteins in the ER.

• Sensors & Functions:

  • IRE1 → Activates XBP1 → ↑ Chaperones, ERAD, lipid synthesis

  • ATF6 → Cleaved in Golgi → ↑ UPR gene expression

  • PERK → Phosphorylates eIF2 → ↓ Translation, ↑ ATF4

Smooth ER and Lipid Synthesis

• Functions:

  • No ribosomes

  • Involved in Lipid metabolism, Detoxification (especially in liver), Calcium storage (e.g., in muscle cells - sarcoplasmic reticulum)

• Lipid Synthesis:

  • Synthesizes Phospholipids – for membranes, Cholesterol & steroid hormones – in liver, adrenal, gonads, Ceramide – precursor to sphingolipids (processed in Golgi)

Synthesis of a Phospholipid

• Starting Material:

  • Glycerol-3-phosphate (from glycolysis), Fatty acyl-CoA (from fatty acid activation

• Process:

  • Fatty acids transferred to glycerol-3-phosphate, forming phospholipid (phosphatidic acid), which is then inserted into the membrane.

• Conversion:

  • Phosphatidic acid converted to diacylglycerol; different polar head groups added for various phospholipids.

• Topography:

  • Synthesis occurs on the cytosolic side, ensuring hydrophobic chains remain buried

Translocation of Phospholipids Across the ER Membrane

• Maintaining Membrane Stability:

  • Newly synthesized phospholipids added to the cytosolic half; flippases facilitate transfer to the lumenal half.

• Flippases:

  • Membrane proteins facilitating rapid translocation, ensuring even growth of both membrane halves

Vesicular Transport From the ER to the Golgi

• Secretory Pathway:

  • Proteins and phospholipids travel through the secretory pathway via transport vesicles.

• Budding and Fusion:

  • Vesicles bud from the ER exit site (ERES) and fuse to form the ER-Golgi intermediate compartment (ERGIC).

• Direction:

  • Cargo moves from ERGIC to the Golgi and between organelles.

Default and Retrieval Pathways

• Default Pathway:

  • Unmarked ER proteins, including resident ones like BiP, are transported to the Golgi.

• Retrieval Pathway:

  • ER-resident proteins are recognized in the ERGIC/Golgi and returned to the ER.

• Retrieval Signals:

  • KDEL Sequence: Directs ER-resident proteins back to the ER.

  • KKXX Sequence: Marks ER transmembrane proteins for retrieval.

The Golgi Apparatus

• Composed of flattened membrane-enclosed sacs (cisternae) and associated vesicles; distinct polarity in structure and function.

• Proteins from the ER enter at the cis (entry) face, oriented toward the nucleus, and are transported through the Golgi, exiting at the trans (exit) face.

• Modification and sorting of proteins during transport for eventual destinations within the cell.

The Golgi Apparatus (Part 1)

• The Golgi apparatus consists of a stack of flattened cisternae corresponding to four regions:

  • cis Golgi network - receives molecules from the ERGIC

  • medial and trans Golgi stacks - most modifications are done here

  • trans Golgi network - the sorting and distribution center

Functions of Golgi Apparatus

• Protein Modification:

  • Glycosylation: Adds and processes carbohydrate groups on proteins (N-linked and O-linked). Example: Glycoproteins involved in cell-cell recognition.

  • Phosphorylation: Addition of phosphate groups (e.g., mannose-6-phosphate tagging for lysosomal enzymes).

  • Sulfation and proteolytic processing may also occur.

• Protein Sorting and Packaging:

  • Proteins are sorted at the trans-Golgi network (TGN) into different vesicles: Secretory vesicles (to the plasma membrane), Lysosomes (via mannose-6-phosphate tagging), Endosomes (regulated secretion).

• Modifies lipids for membrane synthesis and trafficking. Example: Sphingolipid synthesis. Assembles glycolipids and lipid rafts for cell membrane

• Plays a role in the synthesis of complex polysaccharides in plant cells

• Vesicle Formation and Trafficking:

  • Produces transport vesicles coated with: COPI (retrieval to ER), COPII (from ER to Golgi), Clathrin (to endosomes/lysosomes).

  • Ensures directed flow of materials through the secretory pathway

Protein Glycosylation Within the Golgi

• Golgi-mediated protein processing involves extensive modification of glycoproteins.

• Over 250 Golgi enzymes in mammals catalyze the addition of various sugars to glycoproteins.

• N-Linked Oligosaccharide Modification:

  • Proteins initially modified with a 14-sugar residue oligosaccharide in the ER.

  • In the Golgi, three glucose residues are removed, and further modifications (N-acetylglucosamine (GlcNAc), galactose, fucose, sialic acid are added)

Protein Glycosylation Within the Golgi –O-Linked Glycosylation

• O-Linked Glycosylation:

  • Addition of carbohydrates to acceptor serine and threonine residues (O-linked glycosylation).

  • Takes place in the Golgi by sequential addition of single sugar residues.

  • Proteoglycans exemplify extensive O-glycosylation with over 100 carbohydrate chains

Targeting of Lysosomal Proteins by Phosphorylation of Mannose Residues

• Lysosomal Protein Modification:

  • Distinct modification for lysosomal proteins involves mannose phosphorylation.

  • N-acetylglucosamine phosphates added in the cis Golgi compartment.

  • Mannose-6-phosphate residues persist, directing proteins to endosomes and lysosomes.

Lipid and Polysaccharide Metabolism in the Golgi

• The Golgi apparatus not only processes glycoproteins but also plays a role in lipid metabolism and polysaccharide synthesis.

• Synthesis of glycolipids and sphingomyelin occurs in the Golgi, involving ceramide

• Sphingomyelin Synthesis:

  • Sphingomyelin, a nonglycerol phospholipid in cell membranes, synthesized in the Golgi.

  • Process involves transferring a phosphorylcholine group from phosphatidylcholine to ceramide.

• Glycolipid Synthesis:

  • Glycolipids derived from ceramide with added carbohydrates.

  • Glycolipids and sphingomyelin localized to the lumenal half of the Golgi bilayer.

  • Post-vesicular transport, they are positioned on the exterior half of the plasma membrane.

Synthesis of Sphingomyelin and Glycolipids

• Ceramide, which is synthesized in the ER, is converted either to sphingomyelin (a phospholipid) or to glycolipids in the Golgi apparatus.

  • A phosphorylcholine group is transferred from phosphatidylcholine to ceramide. A variety of different glycolipids can be synthesized by the addition of one or more sugar residues (e.g., glucose).

Polysaccharide Synthesis in the Golgi

• Glycosaminoglycans (GAGs):

  • Synthesized in the Golgi lumen.

  • Includes chondroitin sulfate, heparan sulfate, keratan sulfate.

  • Important components of proteoglycans in connective tissue.

• Pectin and Hemicellulose:

  • In plant cells, the Golgi is essential for producing: Pectin: a polysaccharide in the cell wall matrix., Hemicellulose: binds cellulose fibers in plant cell walls.

• Mucopolysaccharides:

  • In animal cells, the Golgi synthesizes mucin-type O-glycans, contributing to mucus and protective glycoproteins.

  • The Golgi apparatus plays a major role in synthesizing and modifying complex polysaccharides, especially for secretion or extracellular matrix assembly.

Protein Sorting and Export From the Golgi Apparatus

• Proteins, lipids, and polysaccharides move from the Golgi to their destinations through the secretory pathway.

• Involves sorting proteins into transport vesicles from the trans-Golgi network

• Transport Routes:

  • Proteins can move to the plasma membrane, lysosomes, vacuoles, or other intracellular destinations.

  • Resident Golgi proteins remain in compartments through signals in their transmembrane and cytoplasmic domains.

  • Some proteins have retrieval signals, similar to ER proteins, ensuring their return to the Golgi.

Transport From the Golgi Apparatus – Plasma Membrane

• Transport to Plasma Membrane:

  • Three routes from the Golgi to the cell surface: Direct transport to the plasma membrane, Transport via recycling endosomes, involved in protein recycling to the plasma membrane, Regulated secretory pathway for specific protein release in response to signals.

Transport to the Plasma Membrane of Polarized Cells

• Epithelial Cell Challenges:

  • Polarized epithelial cells have apical and basolateral domains with specific functions.

  • Proteins leaving the Golgi are selectively transported to these domains via distinct transport vesicles.

  • Sorting to basolateral domains involves amino acid sequences, while apical domains use GPI anchors and carbohydrate modifications.

Transport From the Golgi Apparatus – Lysosome

• Lysosomal Protein Sorting:

  • Lumenal lysosomal proteins marked by mannose-6-phosphates in the Golgi.

  • Trans-Golgi network receptors recognize these residues, leading to packaging into transport vesicles.

  • Yeasts and plant cells lack lysosomes – Proteins are transported from the Golgi to the vacuole, which has the same functions as a lysosome, plus nutrient storage and maintaining turgor pressure. – Proteins are directed to vacuoles by short peptide sequences

The Mechanism of Vesicular Transport

• Involves the movement of proteins, lipids, and other molecules between compartments of the endomembrane system (ER, Golgi, lysosomes, endosomes, plasma membrane).

• Ensures proper sorting, modification, and delivery of cargo.

Types of Transport Pathway

Vesicle Types Involved

Vesicular Transport

• Cargo Selection:

  • Specific receptors or adaptors identify proteins/lipids for transport.

• Vesicle Budding:

  • Vesicle forms by budding from a donor membrane; driven by coat proteins (e.g., COPI, COPII, clathrin).

• Vesicle Scission:

  • Vesicle pinches off with help from GTPases (e.g., dynamin for clathrin-coated vesicles).

• Vesicle Transport:

  • Vesicles move along microtubules using motor proteins (dynein, kinesin).

• Tethering and Docking:

  • Tethering proteins bring the vesicle close to the target membrane; SNARE proteins on vesicle (v-SNARE) and target membrane (t-SNARE) ensure specificity.

• Membrane Fusion:

  • Vesicle fuses with the target membrane to release cargo.

Formation and Fusion of a Transport Vesicle

• Formation of a cytosolic coat results in the budding of a transport vesicle.

• The vesicle is transported by motor proteins along cytoskeletal filaments to its target.

• The transport vesicle then docks at its target membrane, the coat is removed, and the vesicle fuses with its target.

Transport by Coated Vesicles

• Three families of vesicle coat proteins:

  • COPII-coated vesicles:

    • Carry proteins from the ER to the ERGIC and on to the Golgi apparatus.

  • COPI-coated vesicles:

    • Bud from the ERGIC or Golgi and carry their cargo back, returning proteins to earlier compartments.

  • Clathrin-coated vesicles:

    • Transport in both directions between the trans Golgi network, endosomes, lysosomes, and plasma membrane.

Transport by Coated Vesicles Diagram

• Visual representation of COPI, COPII, and Clathrin-mediated transport between the ER, ERGIC, Golgi, endosomes, lysosomes, and plasma membrane.

Formation of a Clathrin-Coated Vesicle

• Regulation by GTP-Binding Proteins:

  • Formation of coated vesicles is regulated by small GTP-binding proteins, Arf and Sar, related to Ras and Ran.

  • Arf functions in the formation of COPI- and clathrin-coated vesicles budding from the Golgi apparatus.

  • Sar functions in the formation of COPII-coated vesicles budding from the ER.

Formation of a Clathrin-Coated Vesicle (contd.)

1. Arf/GDP is converted to the active GTP-bound form.

2. Active Arf/GTP recruits an adaptor protein that initiates cargo selection and coat assembly.

3. Adaptor protein binds to cytosolic domain sequences of transmembrane proteins, signaling their export from the Golgi.

4. Clathrin is recruited, forming a lattice structure that distorts the membrane and initiates vesicle budding.

5. Dynamin, a GTP-binding protein, facilitates membrane fission at the necks of budding vesicles through GTP hydrolysis.

6. Coated vesicles are then ready for transport to their target destinations.

Formation of a Clathrin-Coated Vesicle (Part 2)

• Visual depiction of the assembly of a clathrin-coated vesicle.

Vesicle Fusion

1. Recognition between a vesicle and its target (tethering) mediated by interactions between proteins on the vesicle and target membrane

2. Fusion between the phospholipid bilayers Vesicle fusion is mediated by pairs of transmembrane proteins (SNAREs) on vesicle and target membranes. (v-SNAREs and t-SNAREs).

• SNARE-SNARE pairing provides the energy to bring the two bilayers close enough to destabilize them and fuse

Vesicle Docking and Fusion

• A Rab protein on the vesicle membrane binds to a tethering factor associated with the target membrane.

• This is followed by the formation of complexes between SNAREs on the vesicle and target membranes.

• The coiled-coil domains of the SNAREs zip together, bringing the vesicle and target membranes into close proximity, and the membranes fuse.

Lysosomes

• Lysosomes are membrane-bound organelles containing acid hydrolase enzymes that digest macromolecules.

• Found in animal cells (less prominent in plant cells, where vacuoles perform similar roles).

• Function as the cell’s recycling and degradation center.

• Single membrane.

• Acidic internal pH (~4.5–5) maintained by V-type $H^+$-ATPases.

• Contains over 50 types of hydrolytic enzymes: proteases, nucleases, lipases, glycosidases

Functions of Lysosomes

Lysosomal Storage Diseases

• Caused by deficiency of specific lysosomal enzymes.

• Examples:

  • Tay-Sachs disease – accumulation of GM2 gangliosides.

  • Gaucher disease – accumulation of glucocerebrosides.

  • I-cell disease – failure of M6P tagging; enzymes secreted instead of delivered to lysosomes.

Gaucher Disease

• The enzyme deficiency in Gaucher disease prevents the hydrolysis of glucosylceramide to glucose and ceramide.

Endocytosis and Lysosome Formation

• Endocytosis is the process by which cells internalize extracellular materials via vesicle formation from the plasma membrane.

Endocytosis and Lysosome Formation

• Vesicle Formation

  • Plasma membrane buds inward. Clathrin or other coat proteins help shape vesicles.

• Early Endosome

  • Sorting compartment. Some contents recycled to plasma membrane. More acidic.

• Late Endosome (Multivesicular Body)

  • Fusion with incoming hydrolase-containing vesicles from the trans-Golgi network.

• Lysosome Formation

  • Late endosome matures into a lysosome or fuses with an existing lysosome. Active acid hydrolases degrade cargo. Maintains acidic pH via V-ATPase.

Phagocytosis and Autophagy

• Phagocytosis – External Cleanup:

  • Definition: Uptake of large extracellular particles (e.g., microbes, dead cells).

  • Cell Types: Primarily in specialized cells like macrophages, neutrophils, and dendritic cells.

  • Process: Particle binds to surface receptors, Plasma membrane engulfs the particle → forms a phagosome, Phagosome fuses with a lysosome → forms a phagolysosome, Contents are degraded by acid hydrolases.

  • Function: Defense against pathogens; clearance of debris and dead cells

Autophagy

• The process begins with the enclosure of a small area of cytoplasm or a specific organelle, such as a mitochondrion, inside a membrane structure.

• Lysosomes play a central role in autophagy by fusing with the membrane-bound structures, facilitating the breakdown and recycling of the enclosed cellular components.

Phagocytosis vs Autophagy