MiPsummer Programme pdf - Mitochondrial Physiology Society

58
The Implications of Apolipoprotein E Deficiency on Cardiac Mitochondrial Oxygen
Consumption.
C. Rocha 1 , C. Scheede-Bergdahl 2 and A. Bergdahl 1
1 Department of Exercise Science, Concordia University, Montreal, Canada, 2 Department of
Kinesiology and Physical Education, McGilll University, Montreal, , Canada,
Methods: 2 month old female, age-matched C57Bl/6
(Control) or ApoE-/-- (Experimental) mice
were used. Mitochondrial OXPHOS capacity was measured in permeabilizep
ed cardiomyocytes by
high-resolution respirometry in a cross-sectional design. Mitochondrial content was assessed by
citrate synthase activity and immunoblottings of the
voltage-dependent anion channel. Furtherr
immunoblottings weree done to determine thee relative expressions of o the 5 OXPHOS complexes.
Background: Apolipoprotein E (ApoE) is a class of macromolecules foundd in chylomicrons and
low- and intermediate-density lipoproteins. They are essential for normal n catabolism of triglyceride-
rich substances and are, as such, determinants of lipid metabolism
m. Absence or structural mutations
of ApoE will result
in impaired plasma clearance of cholesterol andd triglycerides. As a
consequence, lipids will be shunted into non-oxidative pathways that ultimately disrupt normal
cellular function.
Objectives: The objective for this project was to determine the effects of disturbed ApoE mediatedd
metabolismm on mitochondrial oxidative capacity.
Results: The in-situ study of mitochondrial
function revealed a highly significant, , 50%
decrease (p=0.002) state 2 respiration (basal, ADPstate
3
restricted) in the ApoE-/- mice whereas the
(maximal, ADP stimulated) respiration was similar
in both groups. Furthermore the respiratory r control
ratio was 15% higher
(p=0.05) in i the heartt tissue
from the ApoE-/- mice while the mitochondrial
leak, estimated as antimycin A flux f subtracted by
oligomycin
flux was reduced by 11% (p=0.05).
Abstract # 29
Conclusion: The results indicate
that lack of ApoE, even in youngg animals, will affect the coupling
between oxidation and phosphorylation within the cardiac mitochondria. Additional work is
necessary to clarify the potential damaging effects
of this reprogramming of bioenergetics.
Modified substrate metabolism followingg a lack of ApoE and subsequent augmentation of
cholesteroll and triglyceride levels, seems to initially
alter the energetic demands off the heart.
Additional
studies need to be performed too define the
functionall underpinnings and whether this
condition ultimately contributes to t heart failure.