Biology: Chapter 6: The mitochondria

What are some main characteristics of mitochondria?

- Diameter of between 0,5 - 1 m - Plastic, mobile organelles. - Found at the sites of intense activity - Divide as the cells divide and replicate with the cell cycle - Predominantly maternally inherited

What are the enzymes in the matrix of the mitochondria required for?

- Enzymes required for the maintenance of the mitochondrial genetic system - Enzymes required for many essential reactions such as the the oxidation of pyruvate and fatty acids, and the citric acid cycle

How is the mitochondria organized into 4 distinct compartments?

- Matrix - Intermembrane space - Inner membrane - Outer membrane

What does the matrix contain?

- Mitochondrial DNA (mtDNA) - Ribosomes - Enzymes

How are mitochondria and chloroplast similar to bacteria cells?

- Their own DNA - Produce many proteins and enzymes - Double membrane - Reproduce like bacteria

What happens after translation of proteins with ER signals?

After translation is completed in the ER, these proteins move via transport vesicles to the Golgi complex; from where they are further sorted to several destinations (secretory pathway): cell surface, lysosome or the plasma membrane Just like the neuropeptides formation in ER to Golgi apparatus in neurons

When are mitochondrial precursor proteins completely folded?

After translocation into their final mitochondrial destination

Who is Lynn Margulis?

American biologist whose serial endosymbiotic theory of eukaryotic cell development revolutionized the modern concept of how life arose on Earth.

What is the mitochondria attached to in the cytoskeleton?

Attached to the microtubules Uses the microtubules to move within the cell to different sites

How could mitochondria with defective oxidative phosphorylation system potentially causing severe damage be countered?

BY promoting changes of mtDNA by mitochondrial fusion and thereby diluting mutations and decreasing negative impact through functional complementation

Why is the mitochondria known as the powerhouse of the cell?

Because it produce most of the energy inside the cell

Why are mitochondria found in greater abundance in muscle cells and neurons?

Because muscle cells and neurons have a greater energy demand

Why is the pH and ion composition in the cytoplasms the same as in the inter membrane space of mitochondria?

Because of the porins in the outer membrane

Why is chaperons required for post-translational processes?

Because polypeptides must have correct folding pattern to function properly, and a completed polypeptide assume correct folding pattern spontaneously, however, before translation is complete it could assume incorrect formation or it could aggregate with other partially made polypeptides, and its the chaperons job to bind nascent polypeptide keeping it from interacting until its completely synthesized

What types of porins does the outer membrane contain?

Beta-barrel type of porins >5kDa

How is mitochondria recycled?

By fission and fusion

How does nuclear proteins enter nuclear membrane?

By having NLS attached to them that are recognized by IMPORTINS that bind to both NLS and NPC (fibrils of channel nucleoporins), and enters nucleus by binding and dissociating to FG-repeats of fibrils

Are most of the proteins in mitochondria encoded by nuclear or mitochondrial genome?

By the nuclear genome

What particular phospholipid is common in the inner membrane of mitochondria?

Cardiolipin

What is the mechanism of mitochondria fission?

Mff and Fis1 anchored on outer mitochondrial membrane recruit Drp1 from cytosol, which then oligomerizes and forms ring-like structure around the mitochondria that constrict and divide it into smaller mitochondria

What is the difference in energy synthesis by the oxidative phosphorylation in the mitochondria and by anaerobic glycolysis?

Mitochondria are able to generate 15 times more ATP from a single glucose molecule than by anaerobic glycolysis

What is the general dynamics of mitochondria?

Mitochondria are very dynamic and plastic organelles Moves about in the cell, constantly changing shape, dividing and fusing

How does mitochondria distinguish itself from the other cytoplasmic organelles?

Mitochondria contain their own DNA

Is import of proteins into mitochondria co- or post-translational?

Post-translational and require chaperone proteins to keep the protein unfolded

What are the mitochondrial precursor proteins?

Proteins that are first fully synthesized as precursor proteins in the cytosol and then translocated into mitochondria, usually seconds or minutes after their release from ribosomes

What are chaperons?

Proteins that avoid other proteins misfiling

What is the secretory pathway?

Rough ER -> Golgi -> secretory vesicles -> cell exterior

What happens if the mutant causing reduced ATP production in the mitochondria exceeds the threshold?

Since the defective oxidative phosphorylation system mitochondria outnumber normal mitochondria, it will affect tissue functions, especially those those that require neurons and muscle cells that require large amount of ATP. Thus, causing serious damage

What is mtDNA heteroplasty level?

The percentage of damaged/mutated DNA within the individual cell

How is protein-chaperone binding and release required?

Through ATP hydrolysis

What is gated transport?

Transport of folded proteins between cytosol and nucleus (topologically equivalent due to NPC). NPC function as selective gates that actively transport specific macromolecules, but also allow some passive diffusion.

What is vesicular transport?

Transport of membrane-encodes intermediated from the ER to the GA, GA to endosome, secretory vesicles and cell exterior, endosomes to lysosomes by active transport. Transport vesicles and fragments are loaded with with a cargo of molecules derived from lumen -> pinched off from its membrane -> discharge their cargo by fusing with other compartment Only between topologically equivalent compartments.

What is transmembrane transport?

Transport of selected proteins from the cytosol into the ER lumen, peroxisomes, plastids (chloroplast) and mitochondria (topologically different spaces) Usually must be unfolded (help from chaperons) to enter through translator (but not for peroxisome). Active transport.

Is translocation active or passive?

active Translocation requires ATP and membrane potential across the inner membrane

How do most peroxisomal proteins cross the peroxisome membrane?

as fully folded proteins

What do the proteins of the inner membrane do?

carry out the oxidation reactions of the electron-transport chain and the ATP synthase that makes ATP in the matrix

What does the cristae junctions contain?

contain special protein complexes that provide a diffusion barrier that segregates the membrane proteins in the two regions of the inner membrane.

What does the cristae membrane contain?

contains the ATP synthase enzyme and large protein complexes of the respiratory chain.

What does the inner boundary membrane contain?

contains the machinery for protein import, new membrane insertion, and assembly of respiratory-chain complexes.

What is cardiolipin?

diphosphatidylglycerol special phospholipid with two covalently linked phospholipid units, with a total of four fatty acid chains instead of two

What is the function of the enzymes in the inter membrane space?

enzymes that use the ATP passing out of the matrix to phosphorylate other nucleotides

What is the matrix of mitochondria?

fluid inside cristae

What are the cristae?

folds in the inner membrane of mitochondria (invaginations)

What does the mitochondrion DNA encodes for?

tRNAs, rRNAs, and some mitochondrial proteins

Mitochondrial fusion requires the coordination of ...

the inner and outer membrane, and their proteins

What is the inner membrane of the mitochondria?

the membrane that surrounds the matrix compartment

What is cristae junctions?

the tubes that joins the inner membrane to the cristae membrane

How is the protein distributed throughout the interior of the mitochondria?

there are a distinct set of proteins in each of the sub compartments in the mitochondria

How do the cristae membrane join the inner membrane

through narrow membrane tubes called cristae junctions

What is oxidative phosphorylation?

useful energy derived from the breakdown of carbohydrates and fatty acids, which is converted to ATP in the mitochondria

What is heteroplasmy?

when a mitochondria contains both mutant and normal genomes

What is homoplasmy?

when all the mitochondria of a cell or tissue have the same genome

What do mitochondrial fission do within the cell?

Facilitate mitochondrial trafficking: by producing multiple smaller mitochondria that are more motile Control maintenance of a healthy pool of mitochondria: segregating dysfunctional mitochondria form healthy counterparts, and damaged mitochondria are subsequently removed by autophagy

What is the endosymbiotic theory?

First eukaryotic cells were formed after an archaea cell engulfed an aerobatic bacterium mitochondria and chloroplasts were once primitive bacterial cells Host cell and ingested bacteria became dependent on each other for survival, resulting in a permanent relationship Due to evolution, mitochondria and chloroplast have specialized and can't live outside the cell

What is mitochondrial fusion and fission?

Fusion: mitochondria fusing Fission: mitochondria dividing

What are the mitofusin 1 and mitofusin 2 (mfn1 and mfn2) protein?

GTPase proteins at the OUTER mitochondrial membrane

What is pumped into the inter membrane space during citric acid cycle? (oxidative phosphorylation)

H+

What is HSP60 and what does it do?

Heat-shock protein 60: interact with proteins imported into the mitochondrial matrix to ensure the proper protein folding

What are the four different protein translocators?

1. The Translocase of the Outer Membrane (TOM) complex. 2. The Sorting and Assembly Machinery (SAM) complex. 3. Two Translocase of the Inner Membrane (TIM) complexes (TIM23 and TIM22). 4. The Oxidase Assembly Machinery (OXA) complex.

What is HSP70 and what does it do?

Heat-shock protein 70: interact with mitochondrial precursor proteins in the cytosol to keep them unfolded before entering the mitochondria They are also located at the matrix space to help the mitochondrial proteins to translocate from the inner membrane into the matrix space

What two types of chaperone families are involved in mitochondrial protein transportation?

Heat-shock proteins 70 and 60 (hsp70 and hsp70)

Where is the pH highest?

Higher pH in the matrix than in the cytosol and the inter membrane space

What neurodegenerative diseases are often related to mitochondrial dysfunction?

Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, and epilepsy. Recent findings also include psychiatric disorders including bipolar disorder and depression.

How do mitochondrial and chloroplast proteins cross the membrane by import?

Partially unfolded form, by the help of chaperons preventing the protein folding

What is the inter membrane space?

narrow region between the inner and outer membranes

How is the passive diffusion through the outer membrane?

outer membrane is freely permeable to ions and to small molecules as large as 5 kDA

What are chaperons?

prevent the protein folding

What is mitochondrial fission factor (Mff)?

protein anchored to outer mitochondrial membrane involved in fission mechanism

What is fission-1 (Fis1)?

protein anchored to the outer mitochondrial membrane involved in fission mechanism

What are the optic atrophy 1 (Opa 1) protein?

protein at the inner mitochondrial membrane

What are porins?

protein channels that span the outer membrane

What is Dynamic-related protein-1 (Drp1)?

protein on outer surface of mitochondria (cytosol) involved in fission mechanism

What happens to signal sequence of mitochondrial proteins once its transported into the matrix?

signal sequence will rapidly be removed after import by a protease in the matrix

What does protein translocation depend on?

signal sequences, chaperons and protein translocators

How does mitochondria recycling works?

1. After use, damaged mitochondria are thought to be recycled by fusion with healthy mitochondria 2. Intra-organelle exchange of proteins, lipids and DNA will occur 3. Subsequent mitochondria fission will generate new mitochondria.

How does proteins move from one compartment to another?

1. By gated transport 2. By transmembrane transport 3. By vesicular transport

Explain the protein synthesis steps:

1. DNA transcription in the nucleus 2. mRNA translated in ribosomes in cytosol 3. tRNA make the protein out of the mRNA in ribosomes in cytosol

What are two functions of mitochondrial fusion?

Dilution of mitochondrial damage (extending lifespan of otherwise non-functional mitochondria) - permits exchanges of mtDNA between functional homeoplasmic and heteroplastic cells Enlargement of mitochondria, offering a larger ATP supply

What is mitochondrial dysfunction?

Imbalanced mitochondrial fission/fusion and an early and common event of neurodegenerative diseases

What does SAM do?

Its located in the outer mitochondrial membrane and helps to fold the proteins properly in the outer membrane

What is TOM required for?

Its located in the outer mitochondrial membrane and is required for the import of all nucleus-encoded mitochondrial proteins. Transport proteins across the outer membrane.

How are most of the mitochondrial precursor proteins recognized by specific receptor proteins that initiate protein translocation?

Most of the mitochondrial precursor proteins have a mitochondrial signal sequence at their N terminus with ability to fold into an amphipathic a helix

What is the mitochondrial signal sequence?

N-terminal (+): 3-5 nonconsecutive Arg or Lys residues, often with Ser and Thr; no Glu or Asp residues

Does heteroplasty always result in disease phenotype?

No, heteroplasty must reach threshold effect and the mtDNA heteroplasty level for the disease to occur. A small percentage of mutation in a cell can give normal phenotype

Does the mitochondria only contain proteins encoded by its own genome?

No. Mitochondria involves proteins encoded by their own genomes and that are translated within itself, as well as proteins encoded by the nuclear genome that are translated on free cytosolic ribosomes and imported from the cytosol into the organelle by specific targeting signals

How does oxidative stress disturb the normal mitochondria cycling?

Oxidative stress within the cell is known to result in mitochondrial fragmentation which disrupts normal mitochondrial cycling.

What is autophagy?

The cell recycles its own organic material. Lysosome will surround it and eat it

What is the multi-chaperone complex?

The metabolite carrier proteins form the large multi-chaperone complex in the cytosol And the multi-chaperone complex is able to dock to the outer membrane receptor, a required step in productive targeting

Once a protein is made, what determines its destination?

The signal sequences in the nascent protein direct its destination The destination could be: ER, lumen of ER, Mitochondria, Nucleus, Peroxisomes

What does TIM 23 and 22 do?

They are located in the inner mitochondrial membrane, and transfer proteins across the inner membrane. Tim 23: transports proteins into the matrix and helps to insert them into the inner membrane Tim 22: mediates the insertion of some inner membrane proteins

what is functional complementation?

Vectors containing a high percent of gene from an organism are individually transformed into a mutant strain until one clone restores the mutant phenotype to wild type (normal type)

What is the threshold effect?

When the damage load exceed the threshold of >60-80 % mitochondrial dysfunction occurs

what is co-translational process?

With ER signal: When a ribosome happens to be making a protein with an ER signal sequence, the signal directs the ribosome to the ER membrane by a co-translational process

What is post-translational process

Without ER signal: When a ribosome happens to be making a protein without an ER signal sequence, the synthesis is completed on free ribosomes and the proteins are released into the cytosol. Then the protein will be directed to its final destination (mitochondria, chloroplasts, nuclei, or peroxisomes) by post-translational processes.

Can mitochondria synthesize proteins internally?

Yes, mitochondria octane DNA and can synthesis some (limited) proteins internally

What is the main function of the cristae?

increase the surface area of the inner membrane and the inner membrane is the site of main activity of the mitochondria

What is the fate of a protein without a sorting signal?

it stays in the cytosol

What is the outer membrane of the mitochondria?

membrane that surrounds the organelle, contains porins

What is mitochondrial fission?

mitocondria division

What is endosymbiosis?

mutually beneficial relationship between a host organism and an internal associate organism.