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Cell Biology > Lecture 7 - Exam 4: Mitochondria > Flashcards

Lecture 7 - Exam 4: Mitochondria Flashcards

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1
Q

What is the main role of the mitochondria?

A

Synthesis of the main chemical energy currency from lipids and carbohydrates: ATP.

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2
Q

Do mitochondria have their own genome?

A

Yes!

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3
Q

Where does the mitchondrial genome come from?

A

The mother

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4
Q

T or F. Mitochondria do not undergo changes in their number and morphology due to the processes of fission and fusion.

A

FALSE…. they do undergo changes by the processes of fission and fusion.

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5
Q

Describe the structure of the mitochondrion.

A

It is organized into four separate functional components.
Has a double membrane system.

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6
Q

T or F. When purified mitochondria are gently fractionated into separate components and their contents are analyzed, a unique collection of proteins exists for each component.

A

TRUE!!

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7
Q

What are the four components of the mitochondrion?

A

Outer membrane, inner membrane, matrix and intermembrane space.

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8
Q

Describe the outer membrane (OM).

A

Aqueous channels through the lipid bilayer (porins), permeable to molecules of 5000 daltons or less (and where the beta barrels are).

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9
Q

Describe the inner membrane (IM).

A

More impermeable than OM, contains proteins that selective transport cargoes into the matrix. It also contains all the elements needed for the synthesis of ATP (ETC and proton pumps)

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10
Q

Describe the Matrix.

A

Contains the genetic system as well as hundreds of enzymes required for oxidation of pyruvate and for the citric cycle (their genome is located here)

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11
Q

Describe the intermembrane space.

A

Enzymes that use the ATP passing out of the matrix to phosphorylate other nucleotides. It also contains proteins that are released during apoptosis. Composition is similar to the cytosol.

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12
Q

What is the principal site of ATP synthesis?

A

The inner membrane

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13
Q

How many NADH and FADH2 are made in the citric acid cycle?

A

3 NADH, 1 FADH2 (these drive the ETC)

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14
Q

The inner membrane is _____% protein.

A

70

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15
Q

Pyruvate (3 C molecule generated during glycolysis in cytosol) and fatty acids are imported from the cytosol and converted to acetyl CoA in the?

A

Mitochondrial matrix

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16
Q

Acetyl CoA is then oxidized to CO2 via the citric acid cycle, coupled to …?

A

The reduction of NAD+ and FAD to NADH and FADH2, respectively.

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17
Q

______________ are transferred through a series of carriers in the inner membrane to molecular oxygen, coupled to the generation of a proton gradient across the membrane.

A

The high energy electrons from NADH and FADH2

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18
Q

Energy stored in the __________ is then used to drive ATP synthesis.

A

proton gradient.

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19
Q

Are mitochondria static?

A

NO! They are constantly dividing and fusing with one another so that they become part of a mitochondrial network.

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20
Q

Fusion = ?

A

Sharing of genetic material within the cell

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21
Q

Fission = ?

A

Making enough mito for cell division and/or increased energy needs.

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22
Q

What is endosymbiosis?

A

Theory of the origin of eukaryotic cells.
Mitochondria are thought to have evolved from bacteria that developed a symbiotic relationship in which they lived with larger cells.

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23
Q

What is the evidence for endosymbiosis?

A
  • Mitochondrial genome are usually circular DNA molecules like those in bacteria, which are present in multiple copies per organelle.
  • The genome most related to the mitochondria genome is the free-living alpha-proteobacteria. They are only able to reproduce within a cell just like mitochondria.
  • Mitochondria can divide like a bacterium. It undergoes a fission process that is conceptually similar to bacterial division.
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24
Q

T or F. Mitochondria are highly dynamic cellular organelles, with the ability to change size, shape and position over the course of a few seconds.

A

True

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25
Q

Mitochondrial Fission:
Two major proteins are involved in mammalian mitochondrial fission. What are they?

A

Fis1 and Drp1 (dynamin related protein) that are on the outer membrane

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26
Q

What is Fis1?

A

An adaptor protein located in the outer membrane, where it is anchored by a C-terminal transmembrane domain.

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27
Q

What is Drp1?

A

Localized in the cytosol, from where it shuttles back and forth to the outer membrane during fission events.

28
Q

How do Drp1 and Fis1 interact?

A

Drp interacts with Fis1 at fission sites, where it is proposed to form a collar that encircles the mitochondrion. This constriction leads fission into two independent organelles.

29
Q

What regulates the site of fission and how fission of the IMM is carried out?

A

Unknown

30
Q

Mitochondrial fusion:
What are the major fusion proteins of mammalian mitochondria?

A

Mfn1 and Mfn2

31
Q

Where are Mfn proteins localized and what do they aid in?

A

Localized to the OMM and aid in the tethering of two mitochondria at the early stages of fusion, through coiled-coil protein interaction domains (sounds like SNAREs, doesn’t it?) Energetically unfavorable

32
Q

What are the Mfn proteins hypothesized to provide?

A

Hypothesized to provide the mechanical forces involved in outer membrane fusion.

33
Q

Other proteins (OPA1, PARL, and mitoPLD) have different roles in ____________.

A

The fusion events, like changing properties of the lipid membrane.

34
Q

Where are mitochondria located near?

A

Sites of high ATP demand

35
Q

The human mitochondrial genomes encodes ___________ involved in electron transport and oxidative phosphorylation.

A

13 proteins

36
Q

How many copies of the genome exist in each mitochondrion?

A

Multiple copies

37
Q

Does the mitochondria genomes or mitochondria proteins encoded by the nuclear genomes have more proteins?

A

Mammalian mitochondria genomes encode only 13 proteins but mitochondria contain around 1500 different proteins encoded by the nuclear genome (99%).

38
Q

Mammalian mitochondria genomes encode only 13 proteins but mitochondria contain around 1500 different proteins encoded by the nuclear genome (99%).
These genes have mostly been transferred to the…?

A

Transferred to the nucleus from the ancestral mitochondrial genome.

39
Q

Mammalian mitochondria genomes encode only 13 proteins but mitochondria contain around 1500 different proteins encoded by the nuclear genome (99%).
These genes have mostly been transferred to the nucleus from the ancestral mitochondrial genome.
These include?

A

-Proteins needed for replication and expression of mitochondrial DNA
-Proteins needed for oxidative phosphorylation
-Enzymes involved in mitochondrial metabolism.

40
Q

The mitochondrial system transcribes what kind of rRNAs and how many tRNAs? What are these required for?

A

Transcribes 16S and 12 S rRNAs and 22 tRNAs, which are required for translation of the proteins in the mitochondria!!

41
Q

What is the mitochondrial ribosome, or mitoribosome?

A

A protein complex that functions as a riboprotein for translating mitochondrial mRNAs encoded in mtDNA.

42
Q

Mitoribosomes, like cytoplasmic ribosomes, consists of how many subunits? What are they?

A

Two subunits: Large (mtLSU) and small (mtSSU).

43
Q

The ratio of __________ is different from ________ ribosomes. Mitoribosomes consist of several…?

A

rRNA/protein ; cytoplasmic
Consist of several specific proteins and less rRNAs.

44
Q

T or F. Codons specify the same amino acids in mitochondria and universal code.

A

False!!! Some codons specify different amino acids in mitochondria than in the universal code.

45
Q

Almost all the mitochondria of fertilized eggs are contributed by the?

A

Ovum, so germ line mutations are transmitted to the next generation by the mother.

46
Q

Mutations in mitochondrial genes are associated with several diseases. What is one?

A

Leber’s hereditary optic neuropathy, which leads to blindness, is caused by mutations in mitochondrial genes that encode components of the ETC. (affects generation of neurons)

47
Q

How can we fix mitochondrial diseases?

A

Mitochondrial replacement therapy.
Take donor egg with normal mitochondria, and remove the donor egg chromosomes. Take the patient egg (with abnormal mitochondria) and insert the patient chromosomes to donor egg. Then fertilize in vitro.

48
Q

Protein Import to Mitochondria:
Most of the proteins are synthesized on _______ and imported to ______________.

A

free ribosomes ; mitochondria as complete polypeptides (goes into the mitochondria already translated) (also coming from the cytosol).

49
Q

Is the import of proteins to mitochondria simple?

A

No, complex because of the double-membrane structure of mitochondria.

50
Q

Protein Import to Mitochondria (sorting to the matrix):
Proteins are targeted to the __________ by amino-terminal sequences (______________).

A

matrix ; mitochondria presequences

51
Q

Describe the Protein import to mitochondria (sorting to the matrix).

A
  1. Unfolded protein associated with Hsp70 chaperones bind to Tom (translocase of the outer membrane) complex. Protein must be unfolded/partially folded!
  2. Protein translocation requires energy.
  3. Proteins are transferred to Tim23 (translocase of the inner membrane)
  4. Presequences are cleaved by matrix processing peptidase (MPP)**, and the polypeptide is bound by other Hsp70 chaperones that facilitate folding
52
Q

What is the alternative for protein import to mitochondria (sorting to the matrix)?

A

Proteins that contain a transmembrane sequence exit Tim23 laterally and insert into IM.

53
Q

What helps drive the import of proteins into matrix?

A

Electrochemical gradient

54
Q

Describe import to mitochondria (sorting to the inner membrane).

A
  • Some proteins with multiple transmembrane domains have internal import signals instead of presequences.
    -After translocation across the outer membrane, they are bound by the Tim9-Tim10 chaperones, which bring them to Tim22 not Tim 23! The protein is transferred laterally into the inner membrane.
55
Q

Describe inner membrane proteins encoded by the mitochondrial genome.

A

-They are synthesized on ribosomes in the mitochondrial matrix and targeted to the Oxa1 translocase in the inner membrane.
-They exit Oxa1 laterally to insert into the inner membrane.

56
Q

Describe import to mitochondria (sorting to outer membrane and intermembrane space).

A

Proteins destined for the outer membrane or intermembrane space also pass through the Tom complex.
-Proteins with single transmembrane domains are inserted via the outer membrane protein Mim1.
-Beta barrel proteins pass through Tom, are bound by Tim9-Tim10 and carried to another translocon called the SAM (sorting and assembly machinery).
-Proteins targeted to the intermembrane space by cysteine-rich sequences recognized by specific chaperones.

57
Q

Mitochondrial Lipids:
Lipids are imported from the..?

A

Cytosol (and coming from the ER and Golgi)

58
Q

Sphingolipids, cholesterol, phosphatidylcholine, phosphatidylinositol, and phosphatidylserine are synthesized where? Where are they transported to?

A

in the ER and transported to the mitochondria by phospholipid transfer proteins.

59
Q

Mitochondria catalyze synthesis of the phospholipid ___________ with 4 fatty acids chains.

A

Cardiolipin (made in the mitochondria)

60
Q

Cardiolipin improves what?

A

Efficiency of oxidative phosphorylation by restricting proton flow across the membrane.

61
Q

Phospholipid transfer proteins extract _________ from the _________ and transport them to the mitochondrial _________ membrane.

A

phospholipid molecules ; endoplasmic reticulum membrane ; outer

62
Q

Phospholipid transfer proteins extract phospholipid molecules form the endoplasmic reticulum membrane and transport them to the mitochondrial outer membrane. This process occurs when mitochondria and ER are ?

A

In close proximity

63
Q

Transfer between inner and outer membrane of the mitochondria happens at sites where ?

A

The membranes touch

64
Q

The transport of small molecules across the inner membrane of mitochondria is mediated by membrane-spanning proteins and driven by the ? Example?

A

electrochemical gradient ;
1 ATP (-4 charge) ** is exported from mitochondria to the intermembrane space and then the cytosol by a transport that exchanges it for 1 ADP (-3 charge)

65
Q

1 ATP (-4 charge) ** is exported from mitochondria to the intermembrane space and then the cytosol by a transport that exchanges it for 1 ADP (-3 charge).
In contrast, the transport of phosphate and pyruvate is …?

A

Coupled to an exchange for hydroxyl ions (OH-)

66
Q

The high pH in the matrix corresponds to more _________, favoring their ___________ to the _________. This is coupled to the transport of _____ and ____ into the matrix.

A

hydroxyl ions ; translocation ; intermembrane space ; phosphate and pyruvate

Cell Biology (33 decks)

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