5.2 Mitochondria Flashcards
How are mitochondria and chloroplast thought to have been produced?
by endosymbiosis
1) unicellular organisms developed mechanism for efficient energy conversion using oxygen (mito) or sunlight (chloro)
2) phagocytosis - at some point organism was consumed by another and didn’t fully digest it.
3) consumed cell continued to survive by predatory cell - beneficial to both.
When one cell is consumed by another w/o fully digesting what might be the benefit?
one is protected inside a larger & presumably more aggressive cell
the other obtained the means for efficient energy.
How does data support the theory of endosymbiosis?
1) both mito & chloro have their own genomes
2) the codon preference & gene structure of these genomes resemble that of modern day bacteria much more than they do most cells
3) physical structure of genome is much like bacteria - simple circular DNA molecules w/no histone packaging mechanism.
How do mito & chloro reproduce their own inside cells?
not linked to divisions of cells. Instead they use a process similar to prokaryotic bacteria called binary fission
what is the process of binary fission?
1) make a number of copies of the circular DNA molecules inside them
2) pinch their whole structure in half - hoping DNA ends up in each half
What would occur if during the pinching process DNA does not make it into one of the daughter cells or organelles?
the daughter cell will simply have a short life span w/in the cell
What is the typical lifespan of mito?
10 days to a few weeks
is mito found in same quantities in every cell?
no, it can be highly variable and depends on a cells energy need. If it needs more energy it will have more mito.
How is mitochondria transferred from one generation to the next?
by transfer of cytoplasm containing mitochondria
Mitochondria and the DNA genome they contain are transferred from one generation to the next through inheritance of egg cytoplam, aka maternal inheritance. Why does this happen?
sperm shed their mitochondria when fertilization of an egg occurs and theyr’e typically not transferred to the resulting embryo
How are diseases linked to mutations in mitochondrial DNA inherited?
all inherited maternally
how are autosomal dominant genes inherited? How does this differ from maternal inheritance
in dominant the dominant gene can be passed to another generation of offsprings through other males or females
in maternal, males do not pass the gene mutation to their children and all affected females receive the mutated gene
How is mitochondrial DNA derived? What does this mean about changes/mutations in DNA?
derived/inherited from a single parent and doesn’t undergo DNA recombination that is typical of the production of egg and sperm
changes in mito DNA arising from natural mutation are inherited in a simple linear manner and can be used to trace the genetic lineage of females over time
Human migration studies using mito DNA can show us what?
can estimate how populations of humans are related to each other and when major separations occured
development of human population back to an original female aka mitochondrial Eve
How many human disease or disorders are linked to mutations in mitochondrial genes? what are they caused by?
over 40 human diseases
caused by alteration to mito proteins through maternal inheritance
Disorders of metabolism are evident in what kind of tissue?
tissue that have high metabolic rates like the heart and muscle tissue
How are genes found in/on host cell chromosomes inovlved in making mito function inherited?
normal mechanisms
what two types of membranes does mitochondria have?
outer mitochondrial membrane - simple
inner mitochondrial membrane - highly specialized b/c it contains ETC and ATP synthase.
What is the name of the space between the mitochondrial inner and outer membrane?
inter-membrane space
What is the space inside the mitochondria called?
mitochondrial matrix
Cristae are most abundant in what type of cell? Why? How is amount regulated?
very energetic cells
cristae increase the inner membrane surface area and the amount of cristae is altered by mitochondria themselves
How are the inner and oute membrane of mito differentiated?
by their protein complexes. Each membrane has proteins unique to them.
Where are most genes and proteins neede for the mitochondria to function produced? How is this issue addressed?
produced outside the mitochondria
to address this issue each membrane has a specific set of transporters that move proteins across or into the mitochondria
What transporters are part of the outer mitochondrial membrane?
TOM (translocase of outer membrane)
SAM (sorting & assembly machine)
What is significant about TOM?
contains receptors that recognize mitochondrial peptides on proteins
all proteins going into a mitochondrion have to interact w/TOM complex in order to get in. TOM is the bouncer
What set of transporters does the inner mitochondrial membrane have?
TIM complexes (translocase of inner membrane)
OXA (oxidase assembly complex)
What happens to the intermitochondrial membrane space when a protein enters?
membranes are folded with assistance of chaperones taht are specific to that space and then the protein can take 3 paths
What path can a protein take when inside intermitochondia membrane?
1) proteins can be INSERTED into the outer membrane by the SAM complex
2) Proteins can be INSERTED into the inner mitochondrial space by the TIM22 complex
3) Proteins can be TRANSLOCATED through inner membrane and into the matrix by TIM 23 complex
What are two ways proteins can end up in the inner mitochondrial membrane itself from the matrix?
1) TIM 23
2) OXA
The OXA complex pathways move protein in the inner mito membrane from the matrix is important for what proteins?
the inner membrane proteins that are encoded for mitochondrial DNA/
How can proteins anchored in the inner mito membrane be released?
by the activity of peptidase leaving the bulk of the protien free in the intermembrane space
Where does the citric cycle take place?
matrix of the mito
What is the job of the citric cycle?
to take complex molecules derived from the digestion of food
to create high energy carrier molecules like NADH
Porins on the outer mitochondrial membrane assist the citric cycle in what way?
create large pores on outer membrane allowing metabolites and phosphonucleotides to pass easily
What does the ionic connection between the intermembrane space of mito and those in the cytoplasm mean?
proteins are different from each space but concentration of things like hydrogen, sodium, calcium, and other small molecules will be identical in both compartments.
Which mitochondrial membrane contains the actual electron transport chain (ETC)
inner mitochondrial membrane b/c remember it’s a specialized membrane
What is the role of the ETC in the inner membrane?
ETC takes high energy molecules from the citric cycle and uses their energy to create a pH gradient w/in the matrix by pumping hydrogen ions across the inner membrane
What does ATP synthase on inner mito membrane do?
converts the pH gradient produced from ETC back into ATP
How are porins formed on the outer mito membrane?
joining of three beta-barrel channels together to form a large pore.
What can and cant pass through the pores on the outer mito membrane?
pass: metabolites, ions, small molecules and small proteins (smaller than 5000 daltons)
not pass: proteins required to remain in intermembrane (so they don’t leak out of cytoplasm)
What produces the energy to generate a proton gradient in mito?
energy of electrons (H+)
ETC pump H+ upward against their concentration gradient
How does the inner membrane form a barrier against the flow of protons?
it contains cardiolipin a “double” phospholipid that is highly impermeable to ions
What does the amount of movement of ions accross a membrane depend on?
the permeability constant of the ion
the area of the membrane
and the concentration gradient
What are the difference between a normal lipid and a cardiolipid?
carbohydrates tails of a cardiolipin are longer
cardiolipin has four tails instead of two like a normal lipid.
What does mitochondria do w/activated electrons from NADH?
add it to oxygen in the presence of hydrogen creating water and releasing ENERGY!
What is the general strategy used by ETC to create a hydrogen gradient?
net rxn: take high energy electrons that are found in part of NADH or NADPH and transfer them to molecular oxygen. This releases energy
What do cells in mito do to conserve energy during ETC and the hydrogen gradient process?
- slow rxn allows for efficient energy conversion
- they don’t release energy all at once in an explosion
- instead the energy of NADH is released gradually in several steps
- each step is used to creat a small addition to hydrogen ion gradien across inner membrane.
What is the net result of releaseing energy slowly during ETC & hydrogen gradient?
6 protons (H+) are moved across the membrane for every molecule of NADH that enters the electron transport chain
1NADH = 6 protons (H+)
In ATP how is the proton gradient created and why?
created by a deficit of protons in the mitochondrial matrix
the intermembrane space is ionically coupled to the cytosol
Name complexes and carriers involved in the ETC
NADH Dehydrogenase Complex
Cytochrome b-c1 complex
cytochrome oxidase complex
Carriers: ubiquinone and cytochrome c
What is the first step in the ETC in mito?
NADH dehydrogenase complex accepts two electrons from NADH producing positively charged NAD+
NADH dehydrogenase passes electrons (2 of them) to ubiquinone one at a time
How many protons are moved out of the matrix in ETC?
one proton for each electron that moves through the complex
ubiquinone’s job in the ETC is to? What step is this?
Step 2 of ETC
-ubiquinone’s job as a lipid soluble carrier of electrons is to pass the electrons from NADH dehydrogenase to a complex called cytochrome b-c1 complex
What happens in ETC after ubiquinone moves electrons to cytochrome b-c1 complex? aka what happens in step 3 of ETC?
electrons move to the cytochromee oxidase complex using soluble carrier cytochrome C
How many proteins does each ETC complex transfer?
1 proton out of the matrix and into the mitochondrial membrane space for every electron that moves through it.
who is the ultimate acceptor of electrons in ETC of mito?
molecular oxygen
electrons are moved from cytochrome oxidase complex by oxygen in rxn 2H+ + 1/2O2 = H2O
How does the mitochondrial ETC make sure no short circuits occur? AKA why isn’t that electrons don’t move directly from NADH dehydro to cytochrome oxidase complex?
each complex of the electron chain contains metal ion cofactor that mediate electron transport : 1) iron sulfur cluster or 2) iron held by ring heme group
lock and key fit between complexes of the ETC brings electron carrier groups close enough to allow transfer
it is ONLY when the complexes of the chain fit together properly does an electron move from one complex to the other and this is why electrons are restricted to moving down the chain from one complex to the next in the right order and they don’t skip any parts of the chain
What are oxygen radicals aka superoxide radicals?
negatively charged oxygen intermediates that are highly reactive and potentially toxic to molecules which can damage cells
What stops superoxide radicals from further damaging cells?
iron copper clusters found w/in the cytochrome c oxidase complex hold onto these superoxidase radicals until a total of four electrons have been transferred to two oxygen molecules which allows water to form & release
Why does the ETC form superoxide radicals?
b/c electrons are moving through the ETC one at a time and therefore at the end of the chain there are intermediate states of oxygen which have absorbed some of the electrons neede to form water but not all
What is one major hypothesis regarding the cause of aging?
the mitochondrial theory of aging
proposes that the accumulation of damage to mitochondrial DNA as a result of the formation of supeoxide radicals eventually compromises the ability of mito to function. Mito DNA is unprotected by conventional DNA protection and repair process.
What is the ATP synthase?
an F-type proton pump which runs backwards (aka instead of using ATP to move protons like a pump would, this complex is using the movement of hydrogen through it to create ATP
What is the structure of ATP synthase??
- large mushroom shaped head (F1) in matrix
- transmembrane domain is the F0 complex
- the Fo + stock make up the rotor that turns when hydrogen ions pass through
The F1 domain head of ATP synthase is held in place by what protein arm?
stentor, which is embedded in the membrane
What happens if you add large excess ATP to the environment around an ATP synthase complex?
you can get it to burn ATP and to spin
How did scientist prove that ATP synthase can spin?
They added actin binding domain to hte stock region of the pump and then attached a short filament of fluorescent actin to it. When they added ATP to the mixture they could watch the stock rotate
How does bacteria move?
they use a similar machine to ATP synthase complex
