mitochondria

mitochondria

useful in energy productions — glucose, glycolysis, and oxidative phosphorylation and CELL DEATH

hvem

can visualize whole cells

mitochondria can have a

branched, circular, spiral, rigid sausage shape

colchicine and nacodolaze

depolarize microtubules

colchicine

causes randon distribution and organization of the mitochondria

microtubules

helps the mitochondria move back and forth

protein synthesis in mitochondria

1. synthesized in mito.

2. cytoplasm to be modifCied

3. shipped back to the mitochondria

mito history

1. first seen under light microscope

2. fist discovered using centrifugation — was found in co-sediment with lysosome

energy production step 1

sodium potassium ATPase — pumps NA+ out of the cell and takes in K+

energy production step 2: SGLT

sodium dependent glucose transport: — brings Na+ out of the cell and takes in glucose

energy production step 3: GLUT transporter

 GLUT10 and GLUT1, are localized to mitochondria, where they regulate mitochondrial metabolism, 

phosphorylation of glucose

makes glucose negatively charged, positions glucose for breakdown, and keeps it in the right spot

phosphorylation of og glucose allows us to

get NADH and convert that into ATP

glycolysis

generates low ATP , does not need oxygen , and happens in the cytoplasm

glycolysis products

2 pyruvate, 2 ATP, and 2 NADH

glycolysis products with no oxygen

lactic acid

mitochondria converts

ADP into ATP

mito outer membrane structure

less proteins, smooth

mito inner membrane: boundary membrane

the inner mito membrane that lies immediately inside and adjacent to the outer membrane

mito inner membrane: cristae junction

the connection between the boundary membrane and the Cristae or middle

cristae

expands surface area

• the site of atp synthesis

outer mitochondrial membrane

contains few proteins and contains porin

porin

a large aqueous channel that allows that passing of smaller molecules

pigbos- a micrprotein

communicates with the ER and regulates the UPR/stress

• decrease in pigbos increases UPR which increases cell death

pigbos- a micrprotein exchanges

Ca 2+ through cross talk & transfers stress signals from the ER to the mitochondria (UPR) using the protein CLCC1

inner mito membrane

contains the electron transport chain

• impermeable

• atp synthase

• larger than the outer membrane

cardiolipin — only in the inner membrane

a 4 legged phospholipid that make membrane impermeable to ions to maintain the gradient

cardiolipin importance

1. glue for mitochondria activity and electron transport proteins

2. increases transmembrane potential by increasing resistance

3. has a role in membrane stability, dynamics, protien import, apoptosis, and atp production

functions of the ER associated mito associated membrane (ER- MAM)

1. calcium concentration maintainence

2. mitochondrial fussion and fussion

fusion

• restores the activity of dysfunctional mitochondria

• homeogeneous process for mitochondria

• mfn1/2 proteins aid the outer membrane fusion while opa1 aids the inner membrane fusion

tem view of mito

black dots = calcium phosphate

fission

• occurs to have an equal distribution of 2 daughter cells

• dpr1 proteins and er “strain” the mito to split

mitochondrial proteins mostly come from

the nuclear protein

heme electron transport component

• is synthesized by the mito gene

• is shipped out by the cytoplasm to be modified

• goes back to the mito

intrinsic mito permeability transition pore cell death

normally mptp is closed but condiitons like chemo or stress force it to open up

when mptp (permeability pore) is open

it is released to cytochrome C - activates apaf 1 — caspase 9 — caspase 3 — then apoptosis occurs

extrinsic mito permeability transition pore cell death

death receptor on cell membrane is activated — caspase 8 is activated — caspase 3 is activated next

bcl 2 — makes up the mptp when it closes

are overexpressed in many cancer cells and are chemo/raditaion resistant

more bcl 2 = closed mptp

no death

open mptp

mitochondria apoptotic cascade is triggered since cytochrome c binds to it

after cytochrome c binds

it goes to the cytoplasm and binds to apaf 1

apaf 1 binds

to procaspase 9 when and creates caspase 9

caspsase 9 binds

procaspase 3 which creates caspase 3

caspase 3

kills the cell — known as the executor enzyme

extrinsic cascade

activates caspase 8 which then leads to apoptosis

bcl 2 — apopto c protein

• was discovered in b cell lymphocytes

• causes resistnace to chemo and radiation

bcl2 treatment : genasense

bcl2 antisense olgionucleotide that targets bcl2 mrna and PREVENTS THE SYNTHESIS OF BCL2

bcl2 treatment : obatoclax

small molecule bcl 2 inhibitor which PREVENTS THE FUNCTION OF BCL2

bcl2 treatment : venetoclax

a bcl2 specific inhibitor that restores apoptosis

• treats patients with chronic lymphatic leukemia CLL

cyclosporin a — immunosuppressant

blocks the mptp from opening and is used to protect stem cells suring storage and transport

hepatocytes

used ofr mitochondrial in vitro toxicity

elesclomol

a drug that triggers apoptosis through targeting the ETC in cancer cells of the mito.

warburg effeect

cancer cells increasing glycolysis rate and decrease oxidative phosphorylation to make more ATP

warburg effeect is the overexpression of

glut 1 and 3

pfk

ldh

mito diseases are plentiful since

the mito comes from the mom

• NO mTDNA which is the micro.’s proofreading dna

mito has

37 genes that code for 13 proteisn and about 1000 to 1500 proteins

mitoc. epilepsy with “raged red fibers”

a neuromuscular disease casued by damamge to the mito.

• characterizzed by progressive myoclonus and seizures

autism

• has been linked to mutations in mtDNA

• inherited from mother and more pronounced in kids with lower IQ

alzheimers disease can come from

accumulation of amyloid beta protien

alzheimers disease can also come from

mito. dysfunction