TY - JOUR

T1 - Cardiac, Skeletal, and smooth muscle mitochondrial respiration

T2 - Are all mitochondria created equal?

AU - Park, Song-Young

AU - Gifford, Jayson R

AU - Andtbacka, Robert H I

AU - Hyngstrom, John R

AU - Garten, Ryan S

AU - Diakos, Nikolaos A

AU - Ives, Stephen J

AU - Dela, Flemming

AU - Larsen, Steen

AU - Drakos, Stavros

AU - Richardson, Russell S

N1 - Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.

PY - 2014/6/6

Y1 - 2014/6/6

N2 - Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15±1 pmol•s(-1)•mg (-1), p<0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac, skeletal, to smooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p<0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal, to smooth muscle, such that the respiratory control ratio (RCR), state 3/state 2 respiration, fell progressively from cardiac, skeletal, to smooth muscle (5.3±0.7; 3.2±0.4; 1.6±0.3, pmol•s(-1)•mg (-1) p<0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscle suggest all mitochondria are created equal, the contrasting RCR and non-phosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially ROS production.

AB - Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial function. Therefore, this study examined mitochondrial respiratory rates in the smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscle. Cardiac, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15±1 pmol•s(-1)•mg (-1), p<0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac, skeletal, to smooth muscle (222±13; 115±2; 48±2 umol•g(-1)•min(-1), p<0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal, to smooth muscle, such that the respiratory control ratio (RCR), state 3/state 2 respiration, fell progressively from cardiac, skeletal, to smooth muscle (5.3±0.7; 3.2±0.4; 1.6±0.3, pmol•s(-1)•mg (-1) p<0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscle suggest all mitochondria are created equal, the contrasting RCR and non-phosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially ROS production.

U2 - 10.1152/ajpheart.00227.2014

DO - 10.1152/ajpheart.00227.2014

M3 - Journal article

C2 - 24906913

VL - 307

SP - H346-52

JO - American Journal of Physiology: Heart and Circulatory Physiology

JF - American Journal of Physiology: Heart and Circulatory Physiology

SN - 0363-6135

IS - 3

ER -