mitochondrial inner membrane lipids and proteins as targets for decreasing cardiac injury Flashcards
lack of blood flow and oxygen to the heart muscle
cardiac ischemia
cardiac tissue damage caused when blood supply returns to the tissue after a period of ischemia
cardiac reperfusion
energy of proton flow back into mitochondrial matrix is used for what ? (3)
regeneration of ATP. replenishment of NADPH. release of energy as heat.
consequence of decline in cellular ion gradients on cellular membrane potential
potential becomes more positive
consequence of decline in cellular ion gradients on action potentials? why?
action potentials shorten because ATP-sensitive potassium channels open
infarction
tissue death due to oxygen deprivation
Increased ___ in early reperfusion primes the permeability transition pore for opening which can be triggered by mitochondrial calcium overload
ROS
basic/acidic pH is observed in ischemia
acidic
acidic pH is thought to increase/decrease PTP opening
decrease
alkaline shift of pH in reperfusion increases/decreases PTP opening
increases. maintenance of acidic pH during reperfusion has been shown to be cardioprotective
hormesis
small dose good, large dose bad
small increases of calcium in the mitochondrial matric can stimulate ____
oxidative phosphorylation
significant calcium overload in the mitochondrial matrix causes ______
collapse of membrane potential
blocking significant mitochondrial calcium influx increases/decreases injury
decreases
Bendavia
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
hexagonal phase
a non-bilayer structure. CL and PE are capable of forming this. common under pH dependent conditions or in presence of divalent cations
hexagonal phase for CL and PE has been observed in cell-free model membrane systems using ?
xray diffraction, 31P NMR, differential scanning calorimetry
Effect of forming hexagonal phase?
high curvature stress, therefore impacting geometry and protein function
CL content and acyl chain composition effects
apoptosis, formation and function of supercomplexes, fusion and fission events
synthesized CL
CL synthase
turnover for CL is much slower/faster than essential inner membrane proteins
faster
CL consists of # acyl chains and # glycerol back bones
4 acyl chains and 3 glycerol back bones
induction of murine diabetes with STZ resulted in a dramatic increase in DHA at the expense of ______
18:2 CL
CL is synthesized from ____ and ____
phosphatidylglycerol and cytidinephospahte-diacylglycerol
common CL fatty acid
linoleic (18:2)
as part of the remodeling process, acyl chains of CL are cleaved, predominately by ? in the heart
phospholipase isoform 2 in the heart. forms monolysoCL
primary enzyme responsible for remodeling monolysoCL
tafazzin
increases/decreases in tafazzin-1 are seen in human heart failure
decreases
knock-down of tafazzin-1 results in a ___ phenotype
cardiomyopathy
tafazzin-1 has a tendency to interact with lipids that form ____ phase
hexagonal phase. explains some CL specificity
MLCLAT and ALCAT
other enzymes responsible for monolysoCL remodeling
Decrease in CL has this effect on ROS
increased ROS production
reduction in CL had this effect on complex 1 and 3 activities
decreased activity. restores by addition of exogenous CL to rat heart preparation.
the presence of ? in the structure of CL renders the lipid highly susceptible to peroxidation
double bonds
increased/decreased CL peroxidation is associated with reperfusion
increased CL peroxidation
increased/decreased CL peroxidation is associated with increased programmed cell death, possibly driven by increased plasma membrane permealization which enhances cytochrome c release
increased CL peroxidation
