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Flashcards in Mitochondrial Genome Deck (106):
1

Mitochondrial DNA is always passed on from the

Mother

2

Which process in the mitochondria generates ATP?

Oxidative Phosphorylation

3

Does not provide nearly as much ATP as oxidative phosphorylation

Anaerobic Phosphorylation

4

What are the four basic components of the mitochondria?

1.) Outer membrane
2.) Intermembrane space
3.) Inner membrane
4.) Matrix

5

The intermembrane space is made up of structural convolutions (fold) called

-The more you have, the more energy you will be able to make

Cristae

6

The oxidative phosphorylation machinery resides in the

Intermembrane space

7

Many of the nuclearly coded proteins residing in the mitochondrial matrix are used for processing

-oxidized within the matrix

Foodstuffs

8

The TCA cycle occurs in the

Mitochondrial matrix

9

Permeable to small molecules but impermeable to large molecules

-contains signaling receptors (Apoptotic receptors)

Outer mitochondrial membrane

10

Contains apoptotic proteins

Inermembrane space

11

Contains transport proteins and is where the electron transport chain takes place.

-It is the ATP synthesizing complex

Inner Mitochondrial membrane

12

Houses the proteins for the TCA cycle, lipid oxidation, transamination, mt DNA, and the mitochondrial protein synthesis machinery

Mitochondrial Matrix

13

Food from our diets (fats, carbs, protein) are metabolized through a process requiring oxygen to generate large amounts of

ATP

14

Says that mitochondria most likely evolved from engulfed bacteria

Endosymbiotic theory

15

There are two different types of mitochondrial proteins. One type, which is made from genomic DNA, and one type which is made from

Mitochondrial DNA

16

In mitochondria, both fission and fusion occur. The fission process is similar to the

Bacterial division process

17

If you start exercising a muscle, you will undergo

Fission

18

Circular DNA, which is proportional to the ATP requirement of the cell

Mitochondrial DNA

19

Mitochondrial DNA codes for 2

rRNAs (16S and 12S)

20

Codes for 22 tRNAs and 13 proteins

Mitochondrial DNA

21

The proteins that the mitochondria encodes are important for

Oxidative phosphorylation

22

The site where most of mitochondrial replication and transcription is controlled

-Allows replication to move faster

D loop (D = displacement)

23

Can replicate independently of the cell cycle

mt DNA

24

Which DNA polymerase functions in mitochondrial replication?

-Encoded by the nuclear genome
-has a proofreading and exonuclease activity
-more error prone than nuclear DNA polymerases

DNA polymerase ƴ

25

What is the helicase for mtDNA replication?

Twinkle

26

There are over 160 identified mutations that lead to disease in

DNA polymerase ƴ or Twinkle

27

Initiated from promoters generating polycistronic transcripts, which are then processed to produce the individual mRNA, rRNA, and tRNA molecules

Mitochondrial Transcription

28

Mitochondrial transcription requires what three things?

1.) mtRNA polymerase
2.) Transcription acticator (TFAM)
3.) Either mtTranscription factor B1 or B2

29

How many RNA polymerases are required for mitochondrial transcription?

1

30

The molecule that helps initiate mitochondrial transcription

-acts almost like a histone after replication

TFAM

31

When TFAM wraps the mtDNA, it becomes a

Nucleoid

32

Organelles about 1 micrometer in length in the cytoplasm of cells. There are typically 10-200 per cell, but there can be thousands of in a cell with very high-energy needs

Mitochondria

33

A typical lipid bilayer, which is permeable to small
molecules (

Outer Mitochondrial Membrane

34

Is the narrow space between the outer and
inner membranes.

-Houses apoptotic molecules, which lead to cell death

Intermembrane Space

35

Has many infoldings known as cristae, which
increase its surface area.

-A most unusual membrane, in having an extremely high protein content and in being impermeable to small as well as large molecules. Even K+ ions, Ca++ ions, ATP, ADP, protons and OH- groups cannot diffuse through

Inner mitochondrial membrane

36

The site of the electron transport chain and of oxidative phosphorylation

The inner mitochondrial membrane

37

The site of the TCA cycle and fatty acid oxidation.

-There are also small circular mitochondrial DNA molecules (mtDNA), which code for 13 polypeptide chains, which are all subunits involved in oxidative phosphorylation, and also for tRNA molecule and ribosomal RNA molecules.

Mitochondrial Matrix

38

The process of oxidative phosphorylation requires about 100 different polypeptide chains. Of these, 13 polypeptide chains are coded for by

mtDNA

39

Mitochondrial protein synthesis uses the rRNAs and tRNAs coded by the mtDNA, but the ribosomal proteins are all coded for by

Nuclear DNA

40

In the mitochondria, replication, transcription, and translation, are all controlled by

Imported nuclear proteins

41

Double stranded circular DNA, made up of 16,600 bases and no introns

Human mtDNA

42

The two strands of mtDNA differe in base composition. What are the two strands of the mtDNA called? Why?

1.) Heavy (H) strand: encodes more proteins
2.) Light (L) strand

43

mtDNA contains only one significant non-coding region, which is called the

D-loop (displacement loop)

44

The site where most of replication and transcription is controlled

D-loop

45

Mitochondria replicate many times in their life cycle. They undergo division by

Fission

46

mtReplication starts with the H strand origin in the

D-loop

47

Binds single stranded DNA in mtDNA replication

mtSSB (mitochondrial single stranded binding protein)

48

Regulated at the non-coding D loop

Mitochondrial transcription

49

Unique in its ability to bind DNA non-specifically in addition to recognising specific sequences within promoter regions

TFAM

50

Packages mtDNA into nucleoids, facilitating
mtDNA replication and transcription, and
provides protection from DNA damage.

TFAM

51

Mitochondrial transcription proceeds bidirectionally, giving rise to

Polycistronic transcripts

52

tRNA processing enzyme that processes mtRNA

RNAse P

53

Human mitochondrial mRNAs have short

Poly(A) tails

54

Translation of the 13 polypeptides coded for by mtDNA takes place in the

Mitochondrial matrix

55

Is mtRNA capped?

No

56

Mitochondrial translation resembles

Bacterial translation

57

What are three distinctive features of mitochondrial genetics?

1.) Very high mtDNA mutation rate
2.) Maternal inheritance of mtDNA
3.) Random segregation of mitochondria and mtDNA

58

Has a DNA mutation rate that is 10-20 times that of nuclear genes

mtDNA

59

Why is mtDNA so prone to mutations?

Because of its proximity to oxidative phosphorylation which generates ROS

60

mtDNA also has no introns and little

Repair mechanism

61

From person to person, the mtDNA sequence differs on average by

4 nucleotides/ 1000 bp

62

The oocyte has a much larger cytoplasmic volume than sperm, so in the fertilized oocyte >99% of mitochondria are contributed by your

Mother

63

The small amount of mtDNA contributed by sperm gets

Inactivated

64

During cell division, mitosis and meiosis ensure coordinated segregation of chromosomes. However, during mitochondrial biogenesis, fission and fusion lead to a

Random distribution of mitochondria and mtDNA

65

When all the mtDNA in a cell are the same, it is known as

Homoplasmy

66

When there is a mixture of mutant and normal mtDNA in the same cell, it is called

Heteroplasmy

67

Tissues such as cardiac muscle, skeletal muscle, and CNS have very high

-each cell has a threshold level

ATP requirements

68

In a heteroplasmic cell, when the number of normal mtDNA drops below the threshold level, the respiration and ATP synthesis of the cell may be insufficient and lead to

Cell death

69

The number of mtDNA mutations increases with age
(especially deletions) and as a result, as you age, the levels of oxidative phosphorylation

-Why older people feel more tired

Decline

70

It is increasingly clear that some human pathological conditions are caused primarily or secondarily by defects in the process of

Oxidative phosphorylation

71

Mutations leading to defects in oxidative phosphorylation can be present either in

mtDNA or Nuclear DNA

72

When the inheritance pattern does not follow simple Mendelian inheritance, we can suspect the possibility of a

-Will have a maternal inheritance pattern

Defect in mtDNA

73

Because of the random distribution of mtDNA, the mutant mitochondria could exceed the threshold in one tissue in one family member, but not in another as a result, we may see

Variability in clinical consequences among family members

74

Maternal inheritance, variability in tissues and among family members, late onset, lactic acidosis, and massive mitochondrial proliferation in myofibers are all clinical features of defects in

mtDNA

75

As we age, there is often an increase in the number of

Mutant mtDNA

76

The most recognized abnormality in patients with mitochondrial disorders is

Lactic acidosis

77

Dysfunction in the ETC causes a decrease in the production of ATP. Low ATP levels result in an upregulation glycolysis, leading to an overproduction of

Lactate

78

Massive mitochondrial proliferation in myofibers appear around the mitochondrial periphery as

Ragged Red Fibers (RRFs)

79

Often include a large part of the mtDNA genome and affect more than 1 subunit

-increases with age, so the disease usually progresses with age

mtDNA deletions

80

Usually spontaneous and sporadic, and have symptoms including: ocular myopathy, lactic acidosis, hearing loss, and dementia

mtDNA deletions

81

Kearns-Sayre syndrome, characterized by progressive muscle weakness and retinopathy is an example of a disease caused by

mtDNA deletions

82

Base substitution mutations in the tRNA of mtDNA result in characteristic

RRFs of mitochondrial myopathy

83

Mutations in the tRNAs usually affect more than one

Subunit

84

A base substitution in the mitochondrial DNA (mtDNA) gene encoding tRNALys is the gene most commonly associated with the disease

MERRF (Monoclonic Epilepsy and Ragged Red Fiber Disease)

85

This mutation that causes MERRF leads to a reduction in mitochondrial protein synthesis, in particular of complexes I and IV, which have the most mitochondrial encoded subunits

A to G substitution at nucleotide 8344

86

A disease characterized by maternal inheritance that is an example of an mtDNA point mutation

Leber's hereditary optic neuropathy (LHON)

87

The death of the optic nerve in LHON results in sudden onset in blindness, and this threshold is crossed when 80-90% of the mtDNA in a cell has the

Mutation

88

Which point mutation is the most common cause of LHON

Arg to HIS substitution in subunit 4 of NADH dehydrogenase

89

Most of the mtDNA point mutations leading to disease are found in

Complex I

90

What are the three different types of mtDNA mutations that lead to disease?

1.) mtDNA deletions
2.) Base substitution mutations in the tRNA
3.) mtDNA point mutations in protein coding genes

91

One major source of mitochondrial diseases is a mutation in the nuclear DNA region coding for

DNA polymerase ƴ

92

Tumor cells adapt to the requirements of unrestrained growth, in part by shifting from oxidative phosphorylation to glycolysis, known as the

-The decreased oxidative phosphorylation is promoted by defects in DNA polymerase POLγ and in mtDNA.

Warburg Effect

93

mtDNA encodes 13 polypeptide chains, which are all part of protein complexes involved in oxidative phosphorylation and are all embedded in the

Inner mitochondrial membrane

94

Four of the five mitochondrial complexes contain

Mitochondrial proteins

95

During early oogenesis, there is a substantial reduction in the amount of mtDNA present. This is known as the

Bottleneck affect

96

There is no mitochondrial division when germ cells are

-results in some cells getting a lot of mutated mtDNA and others getting none

Dividing

97

Can not pass mitochondrial diseases to any of their children

Affected Males

98

The point at which there are enough mtDNA mutations that we begin to see the phenotypic effect

Threshold effect

99

Level of Ox. Phos. decreases with age. When the amount of ATP produced falls below a certain threshold in a given tissue, a phenotype will be observed. This could be due to an increasing number of mutations with age or from

Random distribution of mutated mtDNAs

100

Due to heteroplasmy and the threshold effect,
different tissues harboring the same mtDNA mutation
may be affected to different

Degrees

101

Most mtDNA related sequences share the features of

Lactic acidosis and Massive mitochondrial proliferation (results in RRFs)

102

What two things happen as we age?

# of mtDNA mutations increases, Ox. Phosphorylation decreases

103

Which organs are more frequently affected by mtDNA mutations?

Organs requiring a lot of energy

104

In mtDNA multiple mutations can lead to the same

Disease

105

Only 1/3 of mitochondrial diseases have

RRFs

106

Leigh Syndrome and LHON have no

RRFs

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