Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

Abstract

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 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 to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 μmol·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 nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 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 muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

Keywords: feed arteries; oxidative phosphorylation capacity; respiratory control ratio.

Fig. 1.

Oxidative phosphorylation capacity in cardiac, skeletal, and vascular smooth muscles. Jo₂, O₂ flux. *P < 0.05, smooth muscle vs. cardiac and skeletal muscles; †P < 0.05, smooth muscle vs. skeletal muscle; #P < 0.05, skeletal muscle vs. cardiac muscle. Complex I, complex I state 3 respiration; complex I + II, complex I + II, state 3 respiration.

Fig. 2.

A: relationship between citrate synthase (CS) activity and oxidative phosphorylation capacity (complex I + II, state 3) in cardiac muscle (squares), skeletal muscle (diamonds), and vascular smooth muscle (triangles). P < 0.001. B: oxidative phosphorylation capacity normalized by CS activity, a marker of mitochondrial density, in cardiac, skeletal, and vessel smooth muscles.

Fig. 3.

A: relationship between CS activity and complex IV respiration (N,N,N,N-tetramethyl- p-phenylenediamine + ascorbate) in cardiac muscle (squares), skeletal muscle (diamonds), and vascular smooth muscle (triangles). r = 0.9, P < 0.001. B: oxidative phosphorylation capacity normalized by electron transport capacity.

Fig. 4.

A: complex I state 2 respiration. B: complex I state 2 respiration normalized by CS activity, a marker of mitochondrial density. C: respiratory control ratio, complex I + II, state 3 normalized by complex I state 2 in cardiac, skeletal, and smooth muscles. *P < 0.05, smooth muscle vs. cardiac and skeletal muscles; †P < 0.05, smooth muscle vs. skeletal muscle; #P < 0.05, skeletal muscle vs. cardiac muscle.