Cell Bio Exam #4- The Mitochondria and Peroxisomes

Glycolysis

A catabolic pathway for ATP production that occurs in the cytoplasm

Starts with glucose —> uses some ATP along the way —> generates pyruvate (and some ATP in the form of NADH and FADH2)

An anaerobic process (doesn’t require oxygen)

Produces 2 ATP and 2 NADH

Pyruvate

The product generated from glycolysis

Enters the mitochondria where is generates the molecule acetyl CoA, which is then used to ultimately start the citric acid cycle

Acetyl CoA

A molecule produced by the pyruvate molecule or fatty acid oxidation which acts as the precursor for the citric acid cycle

The citric acid cycle (Krebs cycle)

A catabolic pathway for ATP production that occurs in the mitochondrial matrix

Generates some energy in the form of NADH and FADH2

Pyruvate & acetyl CoA —> ATP released in the form of NADH and FADH2

Acetyl CoA is the major substrate that starts this reaction

Produces 2 ATP, 8 NADH, and 2 FADH2

NADH and FADH2

2 metabolites that acts as a an energy form being produced from the citric acid cycle (kreb cycle)

Broken up in oxidative phosphorylation, producing electrons —> used for oxidative phosphorylation

Change conformation while moving electrons due to the negative charge of the electrons, allowing other proteins to transport protons across the mitochondrial membrane (from the matrix, into the intermembrane space)

Oxidative phosphorylation (electron transport chain)

A catabolic pathway for ATP production that uses the electrons from breaking NADH and FADH2 to make (a lot of) ATP (also produces water from the electron transport chain)

Takes place on the mitochondrial membrane 

An aerobic process (requires oxygen)

Consists of the process of phosphorylating ADP to make ATP

Produces ~32 ATP

Generates an electrochemical concentration gradient across the inner mitochondrial membrane in which there are more protons in the intermembrane space than there are in the matrix, and the only way that the protons can get back through into the matrix is by ATP synthase 

Fatty acid oxidation

A catabolic pathway for ATP production that occurs mostly in the mitochondrial matrix in which ATP is produced from the break of fatty acids

Can occasionally happen in the cytosol —> fatty acids are large molecules and sometimes need to be broken down before reaching the mitochondria

Leads to the generation of acetyl CoA, NADH and FADH2, and thus ATP

Produces hydrogen peroxide from oxygen

Aerobic

Uses oxygen

These processes produce more energy

Anaerobic

Does NOT use oxygen

These processes produce less energy

The mitochondria

An organelle made up of 2 membranes (outer and inner), 2 compartments (intermembrane space and mitochondrial matrix), cristae, and its own genome

Produces ATP

Can be part of a network, or its own entity (they are typically overlap or connected within the cell)

Carry their own ribosomes, meaning they can do translation within

Made up of ~1000-1500 different proteins —> 99% of those proteins are encoded by the nuclear genome (only 13 come from the mitochondrial genome)

Requires proteins essential to the function of this organelle

Parts of its differing membranes overlap each other and connect at some points (phospholipid exchange between the membranes happens at these points)

Outer mitochondrial membrane

One of the two mitochondrial membranes that is smooth and contains holes

Highly permeable (things can pass through relatively easy)

Contains porins

Inner mitochondrial membrane 

One of the two mitochondrial membranes that has a folded structure

Highly impermeable (things can’t pass through)

Contains cristae

Contains the electron transport chain (where oxidative phosphorylation takes place)

Its folded structure allows for a larger surface area that allows for more proteins to pass through and a more efficient electron transport chain

The potential of this membrane drives the import of mitochondrial proteins into the mitochondrial matrix

Intermembrane space

One of the 2 compartments making up the mitochondria

The space in between the 2 mitochondrial membranes

Has a pH of 7 (same as cytosol)

Mitochondrial matrix

One of the 2 compartments making up the mitochondria 

The site of the citric acid cycle

Contains the mitochondrial genome

Contains many enzymes used for the citric acid cycle and fatty acid oxidation

Has a lower pH than the intermembrane space and the cytosol due to the electron transport train

Cristae

The folds in the inner mitochondrial membrane in which the electron transport chain (oxidative phosphorylation) takes place

Provide more surface area for the electron transport chain in order to maximize ATP production

The mitochondrial genome

The genome of mitochondria

A relatively small genome (smaller than a bacterial genome)

There can be multiple copies of this genome within one mitochondria 

Circular DNA molecules (similar to bacteria) in multiple copies

Encodes for 13 proteins used for oxidative phosphorylation, 2 rRNAs, and 22 tRNAs (different from nuclear tRNAs)—> these are all of the necessary components for mitochondrial translation

Mitochondrial fission

Breaking mitochondria apart into 2 (division) by a small GTP binding protein

A single mitochondria divides into two separate organelles

Facilitates cellular distribution of mitochondria during cell division

Allows for isolation and removal of damaged mitochondrial segments

Regulated by proteins such as DRP1 and its receptors (ex. FIS1)

Counterbalances mitochondrial fusion, maintaining organelle dynamics

Critical for mitochondrial quality control and cellular health

Impairing of this process can lead to cellular dysfunction and mitochondrial disease

Mitochondrial fusion 

The coming together of two separate mitochondria into one (they intermix all of their contents, including DNA)

Often leads to multiple mitochondrial genomes in one

Promotes mitochondrial health by compensating for damaged components

Plays a role in cellular energy distribution, ensuring even ATP supply

Regulated by many proteins such as Mfn1 and OPA1

Counterbalanced by mitochondrial fission, maintaining organelle size and number as metabolic environments in the body change

Disruptions in this process can lead to mitochondrial dysfunction and disease

Porins

Protein channels located on the outer mitochondrial membrane that allow smaller molecules (ex. ions, ATP, pyruvate) to flow freely into the intermembrane space

Transmembrane proteins made of beta-sheets (unusual for membrane proteins) —> requires special assembly

Originally made in the cytosol on free ribosomes; they then get imported on their own translocase (MIM and TOM) into the intermembrane space where they get folded by chaperone proteins 

Contain a SAM complex which folds and assembles the beta-barrel structure and inserts it into the outer mitochondrial membrane 

Cardiolipin

A mitochondria-specific phospholipid that is important for generating and shaping the sharp corners of the folds (cristae) of the inner mitochondrial membrane

A key mitochondrial lipid

The structure looks like a dimer of phospholipids —> 2 normal phospholipids fused together which allows them to bend around corners

Exclusive to the inner mitochondrial membrane (only found in the inner membrane)

Vital for optimal mitochondrial function

Plays a role in electron transport chain efficiency (without these phospholipids the inner membrane would be the same as the outer membrane —> less surface area)

Essential for the curvature and stability of the inner membrane

Facilitates protein import into the mitochondria

Involved in apoptosis —> changes can signal cell death

Its deficiency or alteration is linked to various diseases and aging

Apoptosis

A form of programmed cell death

Mfn1 and OPA1

Two proteins out of the many that play a vital role in mitochondrial fusion

DRP1 and FIS1

2 of the many proteins that are vital to the process of mitochondrial fission

The dynamic structure of mitochondria

Mitochondria continually shift between fusion and fission, forming extensive networks or remaining as standalone entities

Alterations in this mitochondrial structuring is linked to neurodegenerative conditions, diabetes, and heart disease (disease connections)

The mitochondrial network

One of the dynamic structures that mitochondria can take on that enables optimal ATP distribution crucial for cellular operations

Allows for genetic material exchange, stress response, calcium signaling, quality control, disease connections, and energy efficiency

Mitochondrial genetic material exchange

The process that regularly occurs in mitochondria that supports mitochondrial health by allowing sharing of mitochondrial DNA 

Is possible due to the dynamic structure and network of mitochondria 

Mitochondrial stress response

A process within mitochondria in which mitochondrial networks adapt to stress, promoting resource sharing and damage resistance

Is possible due to the dynamic structure and network of mitochondria 

Mitochondrial calcium signaling

A mitochondrial process essential for metabolic regulation and apoptosis, facilitated by mitochondrial membranes

Is possible due to the dynamic structure and network of mitochondria 

Mitochondrial quality control

A mitochondrial process in which mitochondrial networking allows for the segregation of damaged mitochondria for repair or removal through mitophagy

Stage 1 of oxidative phosphorylation

A proton gradient is generated by electron transfer through the electron transport chain

Stage 2 of oxidative phosphorylation

ATP is synthesized by proton flow down its gradient through ATP synthase

ATP synthase

An enzyme and channel found in the electron transport chain which allows protons to flow through, down their concentration gradient, into the mitochondrial matrix, causing the enzyme to spin, producing ATP with the help of ADP and phosphates

The final step of the electron transport chain (independent of other steps in the electron transport chain)

Also called complex V

Couples the flow of protons down their gradient to the synthesis of ATP (intermembrane space —> matrix)

Made up of many different proteins that come from different parts of the cell that then are synthesized together to make this complex

Spins within the inner mitochondrial membrane, grabbing ADP and phosphate, allowing it to generate ATP in the mitochondrial matrix 

NADH

A molecule used in many cellular pathways with a proton (H+) attached to it

The detaching of the proton from the enzyme releases electrons and ~10 protons throughout the electron transport chain —> produces less ATP overall as the production of H+ protons leads to less production of ATP

Complex I

A protein complex found in the electron transport chain responsible for detaching the proton from NADH, changing its conformation and allowing for the release and movement of 2 electrons —> leads to the transfer of protons across the inner mitochondrial membrane

Transfers 4 protons across the membrane per NADH molecule

Passes electrons on to coenzyme Q

One of the protein complexes involved in breaking down NADH

Coenzyme Q

An enzyme found in the electron transport chain which receives electrons from complex I, causing it to become reduced

Grabs protons from the matrix and donates them to complex III

Complex III

A protein complex found in the electron transport chain responsible for receiving electrons from coenzyme Q —> this leads to protons being transported into the intermembrane space of the mitochondria

Passes the electrons onto cytochrome c

One of the protein complexes involved in breaking down NADH

Cytochrome c

A molecule located in the intermembrane space of the mitochondria involved in the electron transport chain

Receives electrons from complex III and passes them onto complex IV

Released during the process of apoptosis

Complex IV

A protein complex in the electron transport chain which receives electrons from cytochrome c and then passes protons across the inner mitochondrial membrane and combines the electrons with molecular oxygen, making water as one of the products of oxidative phosphorylation (allows electrons to go back into the mitochondrial matrix)

One of the protein complexes involved in breaking down NADH

Complex II

A protein complex in the electron transport chain that is responsible for passing on electrons produced from the breaking of FADH2 to FAD to coenzyme Q

Does NOT move any protons across the inner mitochondrial membrane

FADH2

A molecule used in many cellular pathways with a proton (H+) attached to it

The detaching of the proton to the molecule produces 0 H+ protons in the electron transport chain —> this allows it to generate more ATP overall

Electrochemical gradient

A word used to describe the electron transport chain

Means a gradient with a charge (caused by the negative charge of electrons) with a proton (H+) involved in the gradient

Drives metabolite (ATP, ADP, phosphates, pyruvate, etc.) transport through transporters in the mitochondrial membrane

cytosol; post-translationally

Most mitochondrial proteins are translated in the ________ and imported __________ into the mitochondria

Mitochondrial tRNAs

A type of RNA produced in the mitochondria

Determines the combinations of the 64 different possible pairings of codons and anticodons (DIFFERENTLY THAN IN NUCLEAR DNA!!!!! —> ex. UGA is stop in the nucleus, AGA is stop in the mitochondria

Mitochondrial replacement therapy

A medical technique used in the UK with the goal of preventing transmission of mitochondrial diseases from mother to offspring

Nuclear DNA from the mother’s egg (with abnormal mitochondria) is combined with healthy mitochondrial DNA from a donor egg resulting in an egg containing nuclear DNA from the mother and mitochondrial DNA from the donor

Making offspring from the DNA of 3 different individuals

The mother’s chromosomes are transferred to the donor egg with the normal mitochondria

Prevents the inheritance of mitochondrial disorders and maintains the genetic link between mother and child

Uses the techniques of maternal spindle transfer (MST) and pronuclear transfer (PNT)

Has many ethical concerns such as, the child has genetic material from 3 individuals, long-term effects and safety concerns, and potential germline modification implications —> this technique is only legal in some countries and there is currently ongoing research on it

Maternal spindle transfer (MST)

One of the two techniques used in mitochondrial replacement therapy

Involves the transfer of the mother’s nuclear DNA into the donor egg with healthy mitochondria

Pronuclear transfer (PNT)

One of the two techniques used in mitochondrial replacement therapy

Involves the transfer of nuclear DNA of the fertilized mother’s egg into a fertilized donor egg with healthy mitochondria

Mitochondrial pre-sequences

Protein sequences, similar to signal sequences, that have specific chemical properties which allow mitochondrial proteins to get recognized and transported to the mitochondria

N-terminal extensions that have positively charged helical structures —> direct mitochondrial proteins to the mitochondria

Get recognized by chaperone proteins, which then brings them, along with the mitochondrial protein, to the mitochondria where they then go through specific complexes depending on where their final destination is 

Bind to receptor sequences on TOM and interact with the TIM23 complex

~70% of all mitochondrial proteins contain one

TOM complex

The transporter complex (translocase) located on the outer mitochondrial membrane

The main entry gate for nuclear-encoded proteins

Recognizes presequences and facilitates protein import

Translocon of the outer membrane

Universal entry point for nearly all mitochondrial proteins

Recognizes hydrophobic targeting signals on proteins

TIM23 complex

The transporter complex (translocase) located on the inner mitochondrial membrane

Transports proteins with presequences into the matrix

Translocon of the inner membrane 

Mitochondrial protein import mechanism (for proteins containing pre-sequences)

1. Presequence binds to receptor site on TOM complex

2. Protein threaded through TOM channel

3. Presequence interacts with TIM23 complex

4. Protein translocated into mitochondrial matrix

5. Presequence cleaved by matrix processing protease (MPP)

• Efficiency in this process ensures mitochondrial functionality

• Dysfunctions in this process are linked to various diseases

• Most mitochondrial proteins have pre-sequences, however some are targeted directly to the inner mitochondrial membrane

Matrix processing protease (MPP)

A protein located in the mitochondrial matrix that cleaves pre-sequences once they have reached the mitochondrial matrix

Requires ATP for the cleavage process

OXA1 Translocase

A distinct translocase protein in the inner mitochondrial membrane responsible for integrating proteins synthesized by mitochondrial ribosomes

Imports some nuclear-encoded proteins into the inner mitochondrial membrane

Specifically used for the 13 proteins that are made from the mitochondrial genome that end up in the electron transport chain  

Protein targeting mitochondrial import mechanism

1. Hydrophobic proteins enter the intermembrane space via the TOM complex

2. Insertion into the inner mitochondrial membrane by the TIM complexes

3. Proteins made in the mitochondria are further integrated by OXA1 translocase

MIM

A translocase specific for importing porins into the outer mitochondrial membrane and then the intermembrane space

SAM complex

A transmembrane protein complex located in the outer membrane of the mitochondria which is responsible for assembling and folding beta-barrel porins and inserting them into the outer mitochondrial membrane 

Sorting and assembling machinery

Phospholipid transfer proteins 

Proteins that transfer phospholipids from the smooth ER (where they are synthesized) to the outer mitochondrial membrane (transfer of phospholipids to the inner mitochondrial membrane is not done by these proteins)

Delivers phospholipids to the outer mitochondrial membrane 

Transfer happens at regions of close contact between the smooth ER and the mitochondria 

Ensures proper liquid composition of mitochondrial membranes 

Facilitates lipid exchange between organelles (ER —> mitochondria)

Helps maintain cellular-lipid homeostasis 

Transporter proteins

Proteins in the inner mitochondrial membrane responsible for the transport of metabolites (such as ATP, ADP, phosphates, and pyruvate) across the mitochondrial membrane

Gets help from the proton gradient —> helps drive metabolites through these protein channels

Sometimes creates a voltage difference across the membrane that drives metabolites through the protein (negative charge from ATP and positive charge from ADP) —> pushes ATP out of the membrane and ADP into the membrane

Some of these proteins get help from the pH difference between the intermembrane space and the matrix —> helps with the exchange of hydroxyl groups for phosphates and pyruvates

NO ACTUAL H+ PROTONS FLOW THROUGH THESE PROTON CHANNELS —> they just get help from the proton gradient to move other molecules across the membrane

Peroxisomes

Small, membrane bound organelles present in nearly all eukaryotic cells

Have many specialized functions, such as fatty acid breakdown, the breaking down of harmful substances like hydrogen peroxide into water and oxygen (detoxification), and the synthesis of phospholipids, specifically plasmalogens (biosynthesis)

Break down fatty acids, generating hydrogen peroxide, which is then also broken down

Has a single membrane

Help with the metabolism of amino acids and uric acid

Cooperate and work with mitochondria and the ER for lipid metabolism

“Helper organelles”

Contain enzymes such as catalase that neutralize toxic compounds (hydrogen peroxide)

Defects in this organelle can lead to rare and serious genetic disorders such as Zellweger syndrome

Contain transmembrane proteins (derived from the peroxisomal ER) and luminal proteins (made on free ribosomes)

Have the ability to undergo fusion and fission

Have the ability to form through the fusion of vesicles budding from the ER —> in this case, cytosolic proteins would be imported into the organelle after its formation

Some existing (old) versions of this organelle can grow and divide (fusion and fission)

Fatty acid breakdown

A process carried out my peroxisomes in which the beta-oxidation (breaking down) of very long chain fatty acids occurs

This occurs before fatty acids are transported to the mitochondria —> this is necessary for larger fatty acid molecules to be able to be transferred to the mitochondria

Produces some metabolites which then need to be taken care of by the peroxisome

Glucose; fatty acids

_______ is the source of most energy, and the main backup is _________

Long-chain fatty acids

Fatty acid molecules that are too large to be broken down by normal enzymes

Must be broken down through fatty acid break down before being transferred to the mitochondria

Plasmalogens

A specialized phospholipid specifically synthesised by peroxisomes through biosynthesis

Contains an ether bond which makes them chemically distinct from typically phospholipids which have ester bonds —> the ether bond also stabilizes the phospholipid allowing it to last longer than a typical phospholipid 

Mostly found in heart and muscle tissues found in the brain

Contribute to the structural fluidity and integrity of cell membranes 

They can act as antioxidants due to their ether bond, protecting cells from oxidative stress

Initially synthesized in the ER and then modified in peroxisomes 

Peroxisomal disorders can impact these specialized phospholipids, leading to reduced levels of them

Reduced levels of these specialized phospholipids have been been associated with various diseases, including Alzheimer’s disease and respiratory distress in neonates

The unique ether linkage at the sn-1 position of glycerol in these specialized phospholipids is more resistant to hydrolysis than ester linkages, providing some protective functions 

A more-stable version of a regular phospholipid

Peroxisomal detoxification

A process done by peroxisomes in which harmful substances such as hydrogen peroxide are broken down into water and oxygen

Peroxisomal biosynthesis

The special synthesis of phospholipids carried out by peroxisomes

Particularly involves the synthesis of plasmalogens

Catalase

An enzyme in peroxisomes that helps to neutralize toxic compounds such as hydrogen peroxide

Decomposes hydrogen peroxide either by the conversion to water and oxygen or by the oxidation of another organic compound

Zellweger disease

A rare and serious genetic disease caused by defects in peroxisomes

Peroxisomal transmembrane proteins

Proteins in the peroxisome derived from the peroxisomal ER through the secretory pathway

Exit the ER through varying vesicles that fuse together creating an import (importomer) complex

Peroxisomal luminal proteins

Proteins in the peroxisome that are made on free ribosomes —> later get imported into the peroxisome through the importomer complex 

Importomer complex

A complex made by the fusing of vesicles that hold transmembrane proteins destined for the peroxisome

Formed by the combination of different proteins 

Allows internal peroxisomal proteins synthesized on cytosolic (free) ribosomes (luminal proteins) to by imported into the peroxisome 

Peroxisomal ER

The part of the ER that generates peroxisomes and peroxisomal proteins

V1 and V2 vesicles

A type of vesicles that carry distinct transmembrane proteins from the ER to the peroxisome

The vesicles often fuse together, resulting in the formation of a functional peroxisome

Peroxisomal matrix proteins

A type of peroxisomal protein that contains the targeting signal PTS1

They get recognized by the cytosolic receptor Pex5

Pex

All peroxisomal proteins go by the general name of ______, followed by a number

Pex5/cargo complex

A protein complex that binds to a docking complex on the membrane of. the peroxisome 

Actin filaments, microtubules, and intermediate filaments 

The three main parts of the cytoskeleton include…

Actin filaments (microfilaments)

One of the three major parts of the cytoskeleton

Provides mechanical support to the cell and determines cell shape

Involved in cell movement and muscle contraction

A cytoskeletal protein and enzyme that is very prominent in all cells —> makes up ~10% of all cells 

Assists in cellular processes such as endocytosis, exocytosis, and cell division (the last stage of cytokinesis —> pinch the two cells off from one another; similar to muscle contraction)

Form the core of cellular extensions such as microvilli (bundles up and supports the microvilli protruding from the cell)

Can grow from both ends and has polarity due to the structure of its monomers

Have dynamic (changeable) structures

Has a nucleotide associated with it that stabilizes it

Can interact with ATP and ADP (ATP is more stable; more energy) —> when bound to ATP it is associated with the rapidly growing barbed end

Has the ability to hydrolyze ATP into ADP —> acts as an ATPase

Typically grows from the barbed end (ATP end), and loses monomers from the pointed end (ADP end)

Doesn’t always need ATP to be built —> comes in different forms; however, if it is associated with ATP, it is more likely to grow from the barbed end and grow faster

When associated with ADP —> monomers dissociate more rapidly from the structure than when associated with ATP

Goes through the process of treadmilling

Get help from many different proteins to form

Can sometimes form a branched structure 

Normally form larger, bundled structures around cells 

The plus ends are capped by proteins at the microvillus tip; the minus ends integrate into the terminal web

Microvilli

Extensions on the top of cells that increase the surface area of the cell allowing for increased intake of nutrients into the cell 

Supported internally by actin filament bundles

Made up by actin filaments that are cross-linked by cross-linking proteins such as villin, fimbrin, and epsin

The plus ends of actin filaments are capped by proteins in the tip

Globular (G) actin

The monomer of actin filaments 

Have tight binding sites that mediate head-to-tail interaction

Come together from particular angles (don’t fit together in a strait line) to form filaments —> creates a “twisting” filament structure

Contain pointed ends and round tops —> when all together in a filament, the pointed ends all line up in the back of the filament

Has directionality due to its barbed end and pointed end (have polarity)

Tropomyosin

A molecule that stabilizes the length of actin filaments by binding lengthwise along the grooves and twisting of the filament

Interacts with actin filaments in specific places (winds around filaments)

An important protein in muscle contractions

Filamentous actin

The structure of an actin filament in which it starts with G actin —> dimer —> trimer —> to a full filament with a pointed end and a barbed end

Can grow at both ends and has polarity

ATPase

A type of enzyme that has the ability to hydrolyze ATP into ADP

Ex. actin filaments

Treadmilling

A process done by actin filaments in which monomers are normally added to the barbed end of the filament, the ATP end, and lost from the pointed end, the less stable ADP end

AEF proteins help with the exchange of ATP for ADP

Profilin; AEF protein

A protein responsible for exchanging ADP —> ATP on actin monomers, promoting actin filament extension 

Helps with the process of actin filament treadmilling

Binds actin monomers and stimulates the exchange of bound ADP for ATP, increasing the concentration of ATP-actin in a filament

The more of this protein there is, the faster actin filaments grow

Nucleation

The process of forming actin filaments

Formin

A molecule necessary for starting the formation of an actin filament —> actin filaments cannot form without this protein 

Binds ATP-actin and starts the initial polymerization of long, unbranched actin filaments 

Comes in a dimer-like structure 

Gathers actin monomers and helps to put them together to form a filament 

Arp 2/3

A protein complex involved in the formation of branches on actin filaments 

Binds to existing filaments and starts a new filament branch allowing the growth of the original branch to continue and the growth of a new filament branch

Capping proteins

Proteins responsible for stabilizing actin filaments by binding to the barbed or pointed ends of the filament

Actin bundles

A structure that actin filaments normal take involving the bundling of actin filaments together

Consists of tightly packed, parallel-arranged actin filaments

Supported by cross-linking proteins that align filaments close together

Allows for better strength and stability of actin filaments

Form structural components of cell surface projections such as microvilli and filopodia

Visible in electron micrographs as dense structures emanating from the actin network

Give rigidity and shape to cell protrusions (ex. microvilli) for interactions with the environment

Filopodia 

A type of cell extension 

Actin networks

A mesh-like arrangement of actin filaments

Forms by the cross-linking by large, flexible proteins that connect intersecting filaments at right angles

Provide a structural framework underneath the plasma membrane

Serve as a versatile scaffold that supports various cell shapes and movements

Offer mechanical support and are involved in dynamic cellular activities, such as motility and shape changes

Cross-linking proteins 

Proteins involved in the formation of actin filament bundles and networks 

Different versions of this protein are used for either the formation of actin bundles or actin networks

Spectrin

A protein normally found in blood cells —> helps give blood cells their shape

An important protein in the plasma membrane

Have tetrameric (4 protein) structures with two alpha (a) and two beta (B) chains

Have actin-binding domains on each B-chain at the the amino (N) terminus

a and B chains include multiple a-helical spacer domains

Forms a network beneath the plasma membrane, cross-linked by short actin filaments

Helps hold up the plasma membrane

Works with cytoskeletal actin filaments

Associate with actin to form a mesh-like network, contributing to the elasticity and mechanical stability of the plasma membrane

Mutations in this protein leads to blood disorders in which blood cells are shaped irregularly, such as hereditary spherocytosis and hereditary elliptocytosis

a-helical spacer domains 

Part of the structure of a spectrin tetramer that provides structural separation between actin-binding domains within the tetramer

Ankyrin

A protein that serves as a critical link between the spectrin-actin network and the plasma membrane by binding to spectrin and a specific transmembrane protein)

Anchors spectrin to transmembrane proteins

Located in the cell membrane —> stuck in place by the cytoskeleton

Contributes to the resilience and shape of red blood cells, allowing them to withstand shear stress in circulation

Defects in this linking component can lead to blood cell deformability issues and are implicated in various hemolytic anemias

Protein 4.1

A protein involved in the reinforcement of the cytoskeleton-membrane linkage

Associates with spectrin-actin junctions and connects to specific transmembrane proteins

Contributes to the resilience and shape of red blood cells, allowing them to withstand shear stress in circulation

Defects in this linking component can lead to blood cell deformability issues and are implicated in various hemolytic anemias

Hereditary spherocytosis and hereditary elliptocytosis

Two diseases associated with mutations in spectrin

Can lead to anemia, jaundice, and an increased risk of gallstones due to the altered shape and reduced lifespan of red blood cells

Impact the spectrin meshwork, compromising the structural integrity of red blood cells and making them more prone to rupture as they pass through the splenic microcirculation

Actin stress fibers 

Contractile bundles of actin filaments that provide structural integrity to the cytoskeleton

Actin filament bundles cross-linked by a-actinin

Work together with focal adhesions to facilitate cell movement and adhesion dynamics

Provide strength and are crucial for cell contractility 

Connect to integrins through complex protein interactions in order to communicate with the inside of the cell

These associations along with all of the proteins involved enable the transmission of mechanical forces and signaling between the extracellular matrix and the cell interior —> critical for cellular processes like migration (cell movement), adhesion (whether a cell sticks to something or not), and cell shaping

Fluorescence microscopy

A cell visualization technique that can be used to view the internal architecture of the cytoskeleton

Focal adhesions

Points of contact between the extracellular matrix and actin filaments

Contain vinculin

Work together with actin stress fibers to facilitate cell movement and adhesion dynamics

Comprised of integrins binding to the extracellular matrix

Vinculin

A protein that helps anchor actin filaments to the cell membrane 

Located at the ends of actin stress fibers

Connects the inside of the cell to the outside environment 

Can be detected using specific antibodies, signifying its presence in focal adhesions 

Plays a crucial role in cell adhesion and signal transduction (picks up messages from the extracellular environment)

Binds to actin filaments, reinforcing the connection between integrins and the cytoskeleton