The mitochondrial-targeted antioxidant, MitoQ, increases liver mitochondrial cardiolipin content in obesogenic diet-fed rats

Abstract

Cardiolipin (CL), a unique mitochondrial phospholipid, plays a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics. The present study was designed to determine the effect of MitoQ, a mitochondrial-targeted antioxidant, on the content of liver mitochondrial membrane phospholipids, in particular CL, and its fatty acid composition in obesogenic diet-fed rats. To do this, twenty-four 6week old male Sprague Dawley rats were randomized into three groups of 8 animals and fed for 8weeks with either a control diet, a high fat diet (HF), or a HF diet with MitoQ (HF+MitoQ). Phospholipid classes and fatty acid composition were assayed by chromatographic methods in liver and liver mitochondria. Mitochondrial bioenergetic function was also evaluated. While MitoQ had no or slight effects on total liver fatty acid composition and phospholipid classes and their fatty acid composition, it had major effects on liver mitochondrial phospholipids and mitochondrial function. Indeed, MitoQ both increased CL synthase gene expression and CL content of liver mitochondria and increased 18:2n-6 (linoleic acid) content of mitochondrial phospholipids by comparison to the HF diet. Moreover, mitochondrial CL content was positively correlated to mitochondrial membrane fluidity, membrane potential and respiration, as well as to ATP synthase activity, while it was negatively correlated to mitochondrial ROS production. These findings suggest that MitoQ may decrease pathogenic alterations to CL content and profiles, thereby preserving mitochondrial function and attenuating the development of some of the features of metabolic syndrome in obesogenic diet-fed rats.

20-Week follow-up of hepatic steatosis installation and liver mitochondrial structure and activity and their interrelation in rats fed a high-fat–high-fructose diet

“…Thus, the increase of CL content during the 1st weeks of HFHFR diet might preserve mitochondrial bioenergetic function. In accordance with that, we and others (12,37,38) have reported increased CL content with HFHFR diet. Increase in CL content may be driven by an increase in overall CL synthesis or a decrease in CL degradation.…”

Cardiolipin remodeling by ALCAT1 links mitochondrial dysfunction to Parkinson’s diseases

“…CL oxidation impairs mitochondrial complex I activity, which is implicated in neurotoxicity and apoptosis in 1‐methyl‐4‐phenyl‐1,2,4,6‐tetrahydropyridine (MPTP) mice (Perier et al, ). In direct support of a causative role of CL peroxidation in the development of PD, mitochondrial‐targeted antioxidants attenuate pathogenesis and protect CL from oxidative damage in mouse models of neurodegenerative diseases (Fouret et al, ; McManus, Murphy, & Franklin, ; Skulachev et al, ).…”

Role of mitochondria and mitochondria‐targeted agents in non‐alcoholic fatty liver disease

“…Feeding rats with a high-fat diet and MitoQ for 8 weeks effectively increased the expression of cardiolipin synthase gene and its level in the liver mitochondria. 87 The MitoQ showed noticeable improvement in the manifestations of metabolic syndrome in rats fed a high-fat diet. 88 Furthermore, previous studies demonstrated the antiapoptotic effect of MitoQ, which was mediated through the inhibition of cytochrome c release and caspase-3 activation.…”