mitochondrial inner membrane lipids and proteins as targets for decreasing cardiac injury

Question 1

lack of blood flow and oxygen to the heart muscle

Answer 1

cardiac ischemia

Question 2

cardiac tissue damage caused when blood supply returns to the tissue after a period of ischemia

Answer 2

cardiac reperfusion

Question 3

energy of proton flow back into mitochondrial matrix is used for what ? (3)

Answer 3

regeneration of ATP. replenishment of NADPH. release of energy as heat.

Question 4

consequence of decline in cellular ion gradients on cellular membrane potential

Answer 4

potential becomes more positive

Question 5

consequence of decline in cellular ion gradients on action potentials? why?

Answer 5

action potentials shorten because ATP-sensitive potassium channels open

Question 6

infarction

Answer 6

tissue death due to oxygen deprivation

Question 7

Increased ___ in early reperfusion primes the permeability transition pore for opening which can be triggered by mitochondrial calcium overload

Answer 7

ROS

Question 8

basic/acidic pH is observed in ischemia

Answer 8

acidic

Question 9

acidic pH is thought to increase/decrease PTP opening

Answer 9

decrease

Question 10

alkaline shift of pH in reperfusion increases/decreases PTP opening

Answer 10

increases. maintenance of acidic pH during reperfusion has been shown to be cardioprotective

Question 11

hormesis

Answer 11

small dose good, large dose bad

Question 12

small increases of calcium in the mitochondrial matric can stimulate ____

Answer 12

oxidative phosphorylation

Question 13

significant calcium overload in the mitochondrial matrix causes ______

Answer 13

collapse of membrane potential

Question 14

blocking significant mitochondrial calcium influx increases/decreases injury

Answer 14

decreases

Question 15

Bendavia

Answer 15

mitochondria targeting peptide. targets due to CL instead of negative membrane ptoential. and at very low concentrations. reduces infarct size, reduces ROS dependent cell death, and improves perfusion when administered prior to reperfusion

Question 16

hexagonal phase

Answer 16

a non-bilayer structure. CL and PE are capable of forming this. common under pH dependent conditions or in presence of divalent cations

Question 17

hexagonal phase for CL and PE has been observed in cell-free model membrane systems using ?

Answer 17

xray diffraction, 31P NMR, differential scanning calorimetry

Question 18

Effect of forming hexagonal phase?

Answer 18

high curvature stress, therefore impacting geometry and protein function

Question 19

CL content and acyl chain composition effects

Answer 19

apoptosis, formation and function of supercomplexes, fusion and fission events

Question 20

synthesized CL

Answer 20

CL synthase

Question 21

turnover for CL is much slower/faster than essential inner membrane proteins

Answer 21

faster

Question 22

CL consists of # acyl chains and # glycerol back bones

Answer 22

4 acyl chains and 3 glycerol back bones

Question 23

induction of murine diabetes with STZ resulted in a dramatic increase in DHA at the expense of ______

Answer 23

18:2 CL

Question 24

CL is synthesized from ____ and ____

Answer 24

phosphatidylglycerol and cytidinephospahte-diacylglycerol

Question 25

common CL fatty acid

Answer 25

linoleic (18:2)

Question 26

as part of the remodeling process, acyl chains of CL are cleaved, predominately by ? in the heart

Answer 26

phospholipase isoform 2 in the heart. forms monolysoCL

Question 27

primary enzyme responsible for remodeling monolysoCL

Answer 27

tafazzin

Question 28

increases/decreases in tafazzin-1 are seen in human heart failure

Answer 28

decreases

Question 29

knock-down of tafazzin-1 results in a ___ phenotype

Answer 29

cardiomyopathy

Question 30

tafazzin-1 has a tendency to interact with lipids that form ____ phase

Answer 30

hexagonal phase. explains some CL specificity

Question 31

MLCLAT and ALCAT

Answer 31

other enzymes responsible for monolysoCL remodeling

Question 32

Decrease in CL has this effect on ROS

Answer 32

increased ROS production

Question 33

reduction in CL had this effect on complex 1 and 3 activities

Answer 33

decreased activity. restores by addition of exogenous CL to rat heart preparation.

Question 34

the presence of ? in the structure of CL renders the lipid highly susceptible to peroxidation

Answer 34

double bonds

Question 35

increased/decreased CL peroxidation is associated with reperfusion

Answer 35

increased CL peroxidation

Question 36

increased/decreased CL peroxidation is associated with increased programmed cell death, possibly driven by increased plasma membrane permealization which enhances cytochrome c release

Answer 36

increased CL peroxidation